Ariel - Volume 12 Number 2

Executive Editors David G. Polin Larry H. Pastor Business Manager Alex Macones Jean Lien Editorial Page Editor Deepak Kapoor Sports Editor Todd Hoover Photography Editors Lois Leach Ken Yonemur

The retail value of the illicit drug market in Italy: a consumption-based approach

This study estimates the retail value of the illicit drug market in Italy from a consumption-based approach. The illicit drugs considered in this analysis are heroin, cocaine, cannabis (herbal and resin), amphetamines and ecstasy. Results show that the value of the illicit drug market in Italy is much less than previously estimated and quantified at \u20ac 3.3 bn. Heroin and cocaine retain the biggest markets in terms of revenues, while cannabis is the most-consumed illicit drug. Synthetic illicit drugs account for roughly 10% of the illicit drug market. Conclusions offer some suggestions as to how uncertainties about estimates of the illicit drug market can be reduced

Inborn errors of OAS–RNase L in SARS-CoV-2–related multisystem inflammatory syndrome in children

International audienceMultisystem inflammatory syndrome in children (MIS-C) is a rare and severe condition that follows benign COVID-19. We report autosomal recessive deficiencies of OAS1 , OAS2 , or RNASEL in five unrelated children with MIS-C. The cytosolic double-stranded RNA (dsRNA)–sensing OAS1 and OAS2 generate 2′-5′-linked oligoadenylates (2-5A) that activate the single-stranded RNA–degrading ribonuclease L (RNase L). Monocytic cell lines and primary myeloid cells with OAS1, OAS2, or RNase L deficiencies produce excessive amounts of inflammatory cytokines upon dsRNA or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) stimulation. Exogenous 2-5A suppresses cytokine production in OAS1-deficient but not RNase L–deficient cells. Cytokine production in RNase L–deficient cells is impaired by MDA5 or RIG-I deficiency and abolished by mitochondrial antiviral-signaling protein (MAVS) deficiency. Recessive OAS–RNase L deficiencies in these patients unleash the production of SARS-CoV-2–triggered, MAVS-mediated inflammatory cytokines by mononuclear phagocytes, thereby underlying MIS-C