Clinical features and comorbidity pattern of HCV infected migrants compared to native patients in care in Italy: A real-life evaluation of the PITER cohort

Background: Direct-acting antivirals are highly effective for the treatment of hepatitis C virus (HCV) infection, regardless race/ethnicity. We aimed to evaluate demographic, virological and clinical data of HCV-infected migrants vs. natives consecutively enrolled in the PITER cohort. Methods: Migrants were defined by country of birth and nationality that was different from Italy. Mann-Whitney U test, Chi-squared test and multiple logistic regression were used. Results: Of 10,669 enrolled patients, 301 (2.8%) were migrants: median age 47 vs. 62 years, (p < 0.001), females 56.5% vs. 45.3%, (p < 0.001), HBsAg positivity 3.8% vs. 1.4%, (p < 0.05). Genotype 1b was prevalent in both groups, whereas genotype 4 was more prevalent in migrants (p < 0.05). Liver disease severity and sustained virologic response (SVR) were similar. A higher prevalence of comorbidities was reported for natives compared to migrants (p < 0.05). Liver disease progression cofactors (HBsAg, HIV coinfection, alcohol abuse, potential metabolic syndrome) were present in 39.1% and 47.1% (p > 0.05) of migrants and natives who eradicated HCV, respectively. Conclusion: Compared to natives, HCV-infected migrants in care have different demographics, HCV genotypes, viral coinfections and comorbidities and similar disease severity, SVR and cofactors for disease progression after HCV eradication. A periodic clinical assessment after HCV eradication in Italians and migrants with cofactors for disease progression is warranted

SARS-CoV-2 Reverse Genetics Reveals a Variable Infection Gradient in the Respiratory Tract

The mode of acquisition and causes for the variable clinical spectrum of coronavirus disease 2019 (COVID-19) remain unknown. We utilized a reverse genetics system to generate a GFP reporter virus to explore severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogenesis and a luciferase reporter virus to demonstrate sera collected from SARS and COVID-19 patients exhibited limited cross-CoV neutralization. High-sensitivity RNA in situ mapping revealed the highest angiotensin-converting enzyme 2 (ACE2) expres-sion in the nose with decreasing expression throughout the lower respiratory tract, paralleled by a striking gradient of SARS-CoV-2 infection in proximal (high) versus distal (low) pulmonary epithelial cultures. COVID-19 autopsied lung studies identified focal disease and, congruent with culture data, SARS-CoV-2-in-fected ciliated and type 2 pneumocyte cells in airway and alveolar regions, respectively. These findings high-light the nasal susceptibility to SARS-CoV-2 with likely subsequent aspiration-mediated virus seeding to the lung in SARS-CoV-2 pathogenesis. These reagents provide a foundation for investigations into virus-host in-teractions in protective immunity, host susceptibility, and virus pathogenesis

Thyroid hormone and glucocorticoid independently regulate the expression of estrogen receptor in male Xenopus liver cells.

Earlier studies from our laboratory had shown that triiodothyronine (T-3) strongly potentiates the activation by estradiol (E(2)) of silent vitellogenin (Vit) genes and the autoinduction of estrogen receptor (ER) mRNA in primary cultures of male Xenopus hepatocytes (Rabelo and Tata, 1993). It was, however, not known if T-3, or other hormones, could up-regulate ER mRNA in the absence of exogenous E(2). We now show that T-3 and dexamethasone (Dex), but not progesterone and testosterone, directly induce ER mRNA within 4 h by separate pathways, at doses compatible with the K-d values of their receptors. This induction of ER mRNA is accompanied by a marked enhancement of the activation of the silent Vit B1 gene if E(2) is added by 12 h after T-3 and Dex, thus suggesting an elevated level of functional ER induced by the two hormones. This conclusion was supported by a higher rate of transcription from an estrogen response element (ERE)-tk-CAT construct transfected into cultured hepatocytes pre-treated with T-3 and Dex before incubation with estrogen. Our findings emphasize the importance of hormonal interplay via auto- and cross-regulation of nuclear hormone receptors

Differential responses to ligands of overexpressed thyroid hormone and retinoid X receptors in a Xenopus cell line and in vivo

In an attempt to explain the contrasting patterns of expression of Xenopus thyroid hormone (xTR) and retinoid X(xRXR) receptor genes and to extend our understanding of the role of heterodimerization of these receptors during amphibian metamorphosis, we have investigated the response to their respective ligands of cells in which xTR and xRXR were overexpressed. Results obtained with two separate approaches are now described. In the first, 3,3',5-triiodothyronine (T-3) was found to strongly upregulate xTR beta mRNA in XTC-2 cells, but not of xTR alpha or xRXR alpha mRNAs, while xRXR gamma transcripts could not be detected. 9-cis-retinoic acid (9-cis-RA) did not substantially influence the expression of any of these four receptor genes. When transcription from three different thyroid response elements (TREs) (a palindromic TREpal, an inverted repeat + 6 [F2] and a direct repeat + 4 [DR + 4] as present in the promoter of xTR beta gene) was measured in XTC-2 cells in which xTR beta and xRXR alpha were overexpressed, only T-3 upregulated transcription while 9-cis-RA, alone or together with T-3, was ineffective. 9-cis-RA however enhanced transcription from an RXR responsive element (RXR-RE). The second approach involved overexpression of xTR beta and xRXR alpha in premetamorphic Xenopus tadpole tail muscle followed by measuring the response of the tails to T-3 in organ culture. After validating the microinjection/culture procedure histochemically, we found that T-3 enhanced transcription from the xTR beta DR + 4 TRE in tails in which xTR beta was overexpressed but the overexpression of xRXR alpha failed to modify this response. It is concluded that in both XTC-2 cells and tadpole tails, overexpressed xRXR fails to modify the enhanced transcriptional response of endogenous and overexpressed xTR beta to T-3 and that exogenous 9-cis-RA is ineffective. Copyright (C) 1997 Elsevier Science Ireland Ltd