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Background: Migrants represent a key target population for viral hepatitis micro-elimination programs and are important targets for specific prevention, screening and treatment programs., Aims: To raise awareness on viral hepatitis among migrants and key stakeholders, assess the prevalence of HBV and HCV among migrants, and determine an optimal and scalable viral hepatitis screening and treatment protocol., Material and Methods: Unselected, consecutive migrants reaching the costs of Italy were screened for HBV, HCV, HDV and HIV markers. Anagraphic and anamnestic information were used to identify viral hepatitis endemic hotspots in the countries of birth or transit. Personal data, including migration route, test results and treatment, were collected and stored in a dedicated database RESULTS: 362 patients were recruited in 2019; median age was 28 years, 71% were male. Most of the patients were African (54%) or Asian (40%). 49% positive for at least one HBV marker: 2.2% HBsAg (asymptomatic carriers with low viremia); 10.6% anti-HBs; 28.5% anti-HBs and anti-HBc, 1.7% anti-HCV, 0.6% anti-HIV, with low or undetectable viral load. Libya was the nexus shared by most of the positive, reactive cases. HCV and HIV markers were only found in migrants already resident in Italy for more than 6-12 months., Conclusion: Low to moderate prevalence of hepatitis B markers were observed in African and Asian first arrival migrants. Migrants positive for HCV and HIV likely acquired the infection after arrival in Italy, suggesting migrants are at risk of contracting viral infections once in Italy, highlighting the importance of ensuring access to prevention for migrant communities., Competing Interests: Declaration of Competing Interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

The CC5 and CXC3 chemokines (CK) pathways are involved in the pathogenesis and outcome of several disease states, including chronic hepatitis C (CHC). The kinetics of Regulated upon Activation Normal T cell Expressed and Secreted (RANTES) (CCL5) and IP-10 (CXCL10) during direct-acting antivirals (DAA) treatment was retrospectively analyzed in 18 liver transplant recipients (LT-R) compared with 20 patients with CHC and 49 healthy controls (HC). CK levels were determined at baseline, week 4, end of treatment, 24 weeks post-treatment (sustained virological response [SVR]), and later-on during follow-up (FU), 12 and 24 months post-DAA. At baseline, median RANTES levels were higher in HC than in both LT-R ( p  > 0.01) and CHC ( p  > 0.01), whereas IP-10 levels were higher in LT-R and CHC than in HC ( p  > 0.05 and p  = 0.01), respectively. Mean RANTES values increased during DAA therapy to peak at SVR and FU with significantly higher levels than at baseline in LT-R ( p  < 0.01) and in CHC, but only at FU ( p  < 0.003). A subsequent return to baseline or lower levels was observed at extended FU. On the contrary, IP-10 values showed a significant decrease from baseline to SVR and FU in both LT-R ( p  < 0.03) and CHC ( p  < 0.01). RANTES profiles during the first 4 weeks of DAA treatment showed an increase or decrease from baseline according to baseline RANTES levels. CCR5 genotyping in LT-R showed the presence of 1 homozygous Δ32/Δ32 and 2 heterozygous WT/Δ32 haplotypes with a prevalence of 5.5% and 11.1%, respectively. In conclusion, although IP-10 showed the expected kinetics, the CC5 pathway appears extensively altered during CHC infection: monitoring these patients may be indicated as they may be at risk of other infections or immune-mediated disorders.

Fenpropimorph (1) is considered a "super high-affinity" σ 1 receptor ligand (K i =0.005nM for guinea pig σ 1 receptors). Here, we examine the binding of 1 and several of its deconstructed analogs at human σ 1 (hσ 1 ) receptors. We monitored their subtype selectivity by determining the binding affinity at σ 2 receptors. In addition, we validated an existing pharmacophore model at the molecular level by conducting 3D molecular modeling studies, using the crystal structure of hσ 1 receptors, and Hydrophatic INTeractions (HINT) analysis. Our structure affinity relationship studies showed that 1 binds with lower affinity at hσ 1 receptors (K i =17.3nM) compared to guinea pig; moreover, we found that none of the fenpropimorph methyl groups is important for its binding at hσ 1 receptors, nor is stereochemistry. For example, removal of all methyl groups as seen in 4 resulted in an almost 5-fold higher affinity at hσ 1 receptors compared to 1 and 350-fold selectivity versus σ 2 receptors. In addition, although the O atom of the morpholine ring does not contribute to affinity at hσ 1 receptors (and might even detract from it), it plays role in subtype (σ 1 versus σ 2 receptor) selectivity., (Copyright © 2017 Elsevier Ltd. All rights reserved.)