Revisiting the role of swine on the risk of Japanese Encephalitis Virus (JEV) transmission in the United States: a rapid systematic review of the literature

Japanese Encephalitis (JE) is an emerging, zoonotic disease transmitted primarily by Culex species mosquitoes (particularly Culex tritaeniorhynchus) carrying the flavivirus Japanese encephalitis virus (JEV). Japanese encephalitis virus maintains its life cycle between mosquitoes and vertebrate hosts, primarily pigs and wading birds (Le Flohic et al., 2013). In humans, JEV infection causes inflammation of the brain (encephalitis) that can cause fever, headache, respiratory distress, gastrointestinal pain, confusion, seizures, and, in some cases, death (Fischer et al., 2012; Hills et al., 2014). The global incidence of JE is uncertain. Effectivity and quality of JE surveillance in endemic countries vary (Jayatilleke et al. 2020), as does availability of diagnostic testing throughout the world. In 2006, the WHO published a position paper on JE vaccines reporting an annual estimation of at least 50,000 new JE cases among those living in countries considered endemic. Campbell et al. (2011) updated prior estimations and predicted a global incidence of JE cases to be nearly 67,900 per year. Most recently, Quan et al. (2020) reported a global estimation of JE incidence of approximately 100,000 per year. Among all clinical cases, children under the age of 10 comprise the majority affected (WHO, 2006). Whereas less than 1% of the cases are accompanied by symptoms, 30% of the symptomatic cases are fatal (Campbell et al., 2011). Furthermore, JE is an untreatable and incurable disease that, once introduced in a community, can lead to devastating economic and health impacts. The United States (US) is considered a susceptible region with great potential for JEV introduction. The availability of competent vectors, susceptible maintenance hosts (avian), intensive travel and trade activities to and from JEV-affected countries, areas with similar climatic and environmental conditions to countries where the virus is epidemic, and large populations of susceptible, amplifying hosts (domestic and feral pigs), makes the US the perfect next-stop in the JEV travel itinerary. In fact, the US is the world’s third-largest producer and consumer of pork and pork products (USDA - ERS). The size of the swine industry in the US can not only be positively correlated with the ability of this virus to invade and establish itself, but also to the impact that an incursion would cause to the economy and the populations’ health. As pigs are considered the main amplifying host of JEV, an extensive review of the literature and identification of knowledge gaps may guide researchers, stakeholders, and policy makers on effort prioritization, development of precautionary intervention measures (to prevent JEV introduction), and evaluation of disease control measures (in case of JEV incursion). Although current conditions have not been favorable for JEV to establish in the US, increases in international trade and globalization, as well as changes in climate and land use, and reductions in pesticide use, can contribute to its rapid and wide geographical spread (Oliveira et al., 2018). A good understanding of the role of swine as an amplifying host for this virus is critical to public health authorities when planning and executing interventions to control the spread of JEV. Therefore, our objectives are 1) to investigate the role of swine on the risk of JEV transmission in the US as an effort for preparedness in the case of an introduction, and 2) to identify knowledge gaps that may serve as a guide to future research efforts

Preparation of Highly Reactive Pyridine- and Pyrimidine-Containing Diarylamine Antioxidants

We recently reported a preliminary account of our efforts to develop novel diarylamine radical-trapping antioxidants (Hanthorn, J. J. et al. J. Am. Chem. Soc. 2012, 134, 8306-8309) wherein we demonstrated that the incorporation of ring nitrogens into diphenylamines affords compounds which display a compromise between H-atom transfer reactivity to peroxyl radicals and stability to one-electron oxidation. Herein we provide the details of the synthetic efforts associated with that report, which have been substantially expanded to produce a library of substituted heterocyclic diarylamines that we have used to provide further insight into the structure-reactivity relationships of these compounds as antioxidants (see the accompanying paper, DOI: 10.1021/jo301012x). The diarylamines were prepared in short, modular sequences from 2-aminopyridine and 2-aminopyrimidine wherein aminations of intermediate pyri(mi)dyl bromides and then Pd-catalyzed cross-coupling reactions of the amines and precursor bromides were the key steps to yield the diarylamines. The cross-coupling reactions were found to proceed best with Pd(η 3-1-PhC 3H 4)(η 5-C 5H 5) as precatalyst, which gave higher yields than the conventional Pd source, Pd 2(dba) 3

Substituted Diarylamines and Use of Same as Antioxidants

This invention relates to substituted heteroaromatic diarylamine compounds which are particularly useful as antioxidant

Incorporation of Ring Nitrogens into Diphenylamine Antioxidants: Striking a Balance between Reactivity and Stability.

The incorporation of nitrogen atoms into the aryl rings of conventional diphenylamine antioxidants enables the preparation of readily accessible, air-stable analogues, several of which have temperature-independent radical-trapping activities up to 200-fold greater than those of typical commercial diphenylamines. Amazingly, the nitrogen atoms raise the oxidation potentials of the amines without greatly changing their radical-trapping (H-atom transfer) reactivity

Substituted Diarylamines and Use of Same as Antioxidants

A compound of Formula I, Formula IA, Formula IB, or Formula II, or an acid or base addition salt thereof, and use of these compounds as antioxidants. In one embodiment, a compound of Formula II, wherein each of X, Y, and Z are independently a carbon or nitrogen atom; R1 and R2 are each independently a hydrogen or an electron donating group, but are not both hydrogen, and wherein R1, and R2 are each bonded to a carbon atom in their own respective aryl ring

HW (Series)

Report describing the experimental facilities of Hanford's Thermal Hydraulics Laboratory, its equipment, personnel, operating schedules, and safety procedures. Appendix begins on page 49

Peroxyesters As Precursors to Peroxyl Radical Clocks

The reactions of peroxyl radicals are at the center of the oxidative degradation of essentially all petroleum-derived hydrocarbons and biological lipids and consequently, the inhibition of these processes by radical-trapping antioxidants. Recently described peroxyl radical clocks offer a simple, convenient, and inexpensive method of determining rate constants for H-atom transfer reactions to peroxyl radicals, greatly enabling the kinetic and mechanistic characterization of compounds with antioxidant properties. We follow up our preliminary communication on the development of a methodology utilizing <i>tert</i>-butyl styrylperacetate as a precursor to a versatile peroxyl radical clock with the present paper, wherein we describe a novel naphthyl analogue, which provides for much improved product resolution for analysis, and provide the complete details associated with its development and application. Using this new precursor, and with consideration of the expanded set of reaction products, inhibition rate constants were measured for a variety of representative phenolic and diarylamine radical-trapping antioxidants. We also provide details for the use of this methodology for the determination of mechanistic information, such as kinetic solvent effects, Arrhenius parameters, and kinetic isotope effects

The Reactivity of Air-Stable Pyridine- and Pyrimidine-Containing Diarylamine Antioxidants

none4siWe recently reported a preliminary account of our efforts to develop novel diarylamine radical-trapping antioxidants (Hanthorn et al. J. Am. Chem. Soc. 2012, 134, 8306−8309), wherein we demonstrated that the incorporation of ring nitrogens into diphenylamines affords compounds that display a compromise between H-atom transfer reactivity to peroxyl radicals and stability to one-electron oxidation. Herein, we report the results of thermochemical and kinetic experiments on an expanded set of diarylamines (see the accompanying paper, DOI: 10.1021/jo301013c), which provide a more complete picture of the structure−reactivity relationships of these compounds as antioxidants. Nitrogen incoporation into a series of alkyl-, alkoxyl-, and dialkylamino-substituted diphenylamines raises their oxidation potentials systematically with the number of nitrogen atoms, resulting in overall increases of 0.3−0.5 V on going from the diphenylamines to the dipyrimidylamines. At the same time, the effect of nitrogen incorporation on their reactivity toward peroxyl radicals was comparatively small (a decrease of only 6-fold at most), which is also reflected in their N−H bond dissociation enthalpies. Rate constants for reactions of dialkylamino-substituted diarylamines with peroxyl radicals were found to be >107 M−1 s−1, which correspond to the pre-exponential factors that we obtained for a representative trio of compounds (log A ∼ 7), indicating that the activation energies (Ea) are negligible for these reactions. Comparison of our thermokinetic data for reactions of the diarylamines with peroxyl radicals with literature data for reactions of phenols with peroxyl radicals clearly reveals that diarylamines have higher inherent reactivities, which can be explained by a proton-coupled electron-transfer mechanism for these reactions, which is supported by theoretical calculations. A similar comparison of the reactivities of diarylamines and phenols with alkyl radicals, which must take place by a H-atom transfer mechanism, clearly reveals the importance of the polar effect in the reactions of the more acidic phenols, which makes phenols comparatively more reactive.noneJ. Hanthorn; R. Amorati; L. Valgimigli; D. PrattJ. Hanthorn; R. Amorati; L. Valgimigli; D. Prat

Preparation of Highly Reactive Pyridine- and Pyrimidine-Containing Diarylamine Antioxidants

We recently reported a preliminary account of our efforts to develop novel diarylamine radical-trapping antioxidants (Hanthorn, J. J. et al. J. Am. Chem. Soc. 2012, 134, 8306−8309) wherein we demonstrated that the incorporation of ring nitrogens into diphenylamines affords compounds which display a compromise between H-atom transfer reactivity to peroxyl radicals and stability to one-electron oxidation. Herein we provide the details of the synthetic efforts associated with that report, which have been substantially expanded to produce a library of substituted heterocyclic diarylamines that we have used to provide further insight into the structure–reactivity relationships of these compounds as antioxidants (see the accompanying paper, DOI: 10.1021/jo301012x). The diarylamines were prepared in short, modular sequences from 2-aminopyridine and 2-aminopyrimidine wherein aminations of intermediate pyri­(mi)­dyl bromides and then Pd-catalyzed cross-coupling reactions of the amines and precursor bromides were the key steps to yield the diarylamines. The cross-coupling reactions were found to proceed best with Pd­(η³-1-PhC₃H₄)­(η⁵-C₅H₅) as precatalyst, which gave higher yields than the conventional Pd source, Pd₂(dba)₃