Iran, Pakistan, Iraq, Qatar and the United Arab Emirates were the main countries that saw an increase in heroin use in 2015 and 2016 [1]. This increase was linked to the expanding of heroin trafficking from Afghanistan to these countries. Other countries such as Saudi Arabia, Jordan and Israel saw stabilization in heroin use, as stimulants are playing a larger role in these countries currently. On the other hand, some countries in East and South-East Asia saw a decline in heroin use in 2016 such as China, Indonesia, Thailand, the Republic of Korea and Hong Kong [1].
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Pharmacists play a vital role in the implementation of THN strategies. Barriers that were identified to pharmacists providing naloxone education included time constraints, inadequate training, perceived lack of patient comprehension [36, 37], and lack of pharmacist prescribing privileges [38, 39]. A collaborative practice approach between prescribing physicians and pharmacists can be adopted to solve this issue by providing pharmacists with the necessary privileges to dispense naloxone through pre-authorized orders on the electronic health record system that they may activate. Stakeholders can play an important part in facilitating such policy reform efforts, and fighting community stigma and resistance [38, 39]. Targeted naloxone training in smaller chain pharmacies may be necessary as well [40], and structural changes in the level of insurance coverage to compensate pharmacists for brief interventions such as counseling on substance use, and naloxone administration training may be required as well [38].
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The evolutionarily conserved signaling pathway, Delta-Notch, plays crucial roles in embryonic development, stem cell maintenance and adult tissue renewal [76]. While the Delta-Notch signaling pathway was well described for its role in developmental processes, a recent study has reported a new role of the Delta-Notch signaling pathway in antiviral innate immunity in the mosquito, by limiting the replication of DENV in Ae. aegypti mosquitoes [77]. Notch is a transmembrane receptor and signaling depends on the binding of Delta ligands, which activates the proteolysis of the Notch receptor, releasing an active fragment, known as the Notch intracellular domain (NICD) that enters the nucleus to activate downstream target genes [76, 78]. During DENV infection, components of this pathway including Delta, Notch and Hindsight genes were also shown to be upregulated in Ae. aegypti mosquitoes [77]. Although the exact mechanism of how this signaling pathway limits DENV replication is not known, this study showed that activation of this signaling pathway induced endoreplication, in which cells undergo many rounds of DNA replication without mitosis to increase dramatically the genomic DNA content in the cells. Induction of endoreplication increased the number of gene transcripts that are involved in controlling viral spread [77].
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