17,β-estradiol inhibits hepatitis C virus mainly by interference with the release phase of its life cycle

Rationale & Aim: Estrogen and estrogen-mediated signalling protect from hepatitis C virus through incompletely understood mechanisms. We aimed to ascertain which phase(s) of HCV life cycle is/are affected by estrogens. Methods: Huh7 cells infected with the JFH1 virus (genotype 2a) were exposed to dehydroepiandrosterone, testosterone, progesterone and 17β-estradiol (tested with/without its receptor antagonist fulvestrant). Dose-response curves were established to calculate IC50 values. To dissect how 17β-estradiol interferes with phases of HCV life cycle, its effects were measured on the HCV pseudo-particle system (viral entry), the sub-genomic replicon N17/JFH1 and the replicon cell line Huh7-J17 (viral replication). Finally, in a dual-step infection model, infectious supernatants, collected from infected cells exposed to hormones, were used to infect naïve cells. Results: Progesterone and testosterone showed no inhibitory effect on HCV; dehydroepiandrosterone was only mildly inhibitory. In contrast, 17β-estradiol inhibited infection by 64-67% (IC50 values 140 to 160 nM). Fulvestrant reverted the inhibition by 17β-estradiol in a dose-dependent manner. 17β-estradiol exerted only a slight inhibition (<20%) on HCV pseudo-particles, and had no effect on cells either transiently or stably (Huh7-J17 cells) expressing the N17/JFH1 replicon. In the dual-step infection model, a significant IC50 decline occurred between primary (134 nM) and secondary (100 nM) infections (p=0.02), with extracellular HCV RNA and infectivity being reduced to a higher degree in comparison to its intracellular counterpart. Conclusions: 17β-estradiol inhibits HCV acting through its intracellular receptors, mainly interfering with late phases (assembly/release) of the HCV life cycle

T-cell mediated responses against alpha-foetoprotein in hepatocellular carcinoma: Relationship with hepatitis C virus infection, tumour phenotype and patients’ survival

Background Alpha-foetoprotein (AFP) is a potential immunotherapeutic target in hepatocellular carcinoma (HCC). However, T-cell response (TR) to AFP is suppressed in HCC due to immune evasion. It is unknown whether HCV infection may pre-condition TR against AFP, or whether TR may influence the clinical course of HCC. Methods We prospectively enrolled 18 HCV+ treatment-naïve patients with cirrhosis (CC), 18 HCV+ HCC cases and 17 HCV- HCC cases. TR was quantified by ELISPOT using assays specific to interleukin (IL) 2, IL10 and granulocyte-monocyte colony stimulating factor (GM-CSF) on ex-vivo peripheral blood mononuclear cells (PBMC) stimulated in vitro with AFP peptides. Cytokine ratios were compared between groups and with clinicopathological features of HCC, including overall survival (OS). Results The proportion of AFP-specific responses was not different across the studied groups for any of the assayed cytokines. AFP-specific IL-2 responses were increased in larger (P = .02), multifocal tumours (P = .01) and correlated with advanced disease (P = .01). TRs did not correlate with other clinicopathological factors and did not predict for OS. Conclusion Tumour stage but not HCV infection is related to the emergence of anti-AFP TRs. These data enable formulation of a rationale for the further development of anti-AFP immunotherapy in HCC, facilitating optimal patient selection for future studies

IAU Office of Astronomy for Education, OAE Center Italy - Annual Report 2021

First annual report of the the IAU OAE Center Italy, an international office addressed to education and hosted and financed by Inaf. OAE Center Italy was established on the 3rd of March 2021, thanks to a Memorandum of Understanding signed by three parties: IAU, the Office of Astronomy for Education and INAF. OAE Center Italy is a joint project of a consortium of Italian partners, led and represented by INAF and of the IAU OAE, and is operated by INAF. The Italian partners are INAF, the Italian Astronomical Society (SAIt) and the University of Rome Tor Vergata (ToV)

Macchine del Tempo/Time Machines Concept per la realizzazione di una grande mostra INAF nella città di Roma

La Mostra “Macchine del Tempo/Time Machines” sarà inaugurata a fine 2023, si chiuderà a Primavera del 2024 e verrà ospitata nel secondo piano del Palazzo delle Esposizioni di Roma, in Via Nazionale, gestito dall’Azienda Speciale Palaexpo, una partecipata del Comune di Roma, con cui sarà siglata una specifica convenzione. Il progetto ha un duplice obiettivo, da un lato realizzare una mostra pop che parli a tutti e che metta al centro l’Istituto Nazionale di Astrofisica, le sue persone e le sue ricerche, dall’altro dar vita a qualcosa di unico, che faccia parlare di sé e che incentivi il pubblico a informarsi sulle tematiche affrontate per ampliare il proprio sapere e conoscere INAF e i suoi osservatori distribuiti sul territorio italiano. Un percorso che vuole giocare tra il vecchio e il nuovo, con uno stile anni ’80, ma con contenuti che parlano dell’oggi e del domani e che usa il gioco come meccanismo per suscitare interesse ed emozione positiva. Le “Macchine del Tempo” sono strumenti dell’ingegno italiano, frutto della ricerca condotta negli osservatori dell’Istituto Nazionale di Astrofisica dalle donne e dagli uomini che ogni giorno mettono impegno e passione per portare le conoscenze umane sempre più distanti. Questa mostra vuole diffondere la conoscenza attuale facendo però vedere chi c’è “dietro l’oculare”. Un’esperienza immersiva che comincia da noi stessi e subito passa a Galileo, l’italiano che - inventando il cannocchiale - posò l’occhio sulla nostra prima “macchina del tempo”. Sarà importante realizzare un catalogo della mostra e sono stati avviati contatti per rendere l’esposizione fruibile al pubblico in modo quanto più possibile inclusivo. Nel corso del periodo in cui sarà visitabile la mostra saranno organizzati incontri scientifici di alto livello, con nomi di primo piano della Ricerca astrofisica e spaziale mondiale, ma anche aperitivi scientifici più informali, durante i quali i cittadini potranno conversare direttamente con i ricercatori. Verranno proposti dei progetti di public engagement che utilizzano format nuovi come il Poetry Slam abbinato a uno stage scientifico o rassegne cinematografiche che propongono film nei quali sono presenti strutturei INAF. Si intende inoltre realizzare uno show per planetario, in collaborazione con il Planetario di Roma, sul tema “Macchine del Tempo”, da programmare in un periodo vicino a quello della della mostra e da diffondere in seguito, anche sotto forma di film per planetario, sia in italiano che in altre lingue, per la fruizione da parte di un pubblico internazionale. La mostra “Macchine del Tempo” ha per INAF molteplici aspetti di ritorno in campo sociale, comunicativo e relazionale. La mostra vuole stimolare le giovani generazioni allo studio di materie STEM, ma con “contaminazioni” anche di altre discipline non solo scientifiche. Questo determinerà in futuro per INAF anche la possibilità di avere giovani risorse da inserire nell’organico di ricerca. L’astrofisica italiana è un'eccellenza internazionalmente riconosciuta e deve essere maggiormente valorizzata anche in Italia, per potenziare l’immagine che INAF trasmette ai cittadini, alle istituzioni e agli stakeholders, attraverso i finanziamenti pubblici rivolti alla ricerca, incentivando ad esempio le collaborazioni, o anche le donazioni, con altre realtà pubbliche o private. Questa mostra vuole essere un mezzo per offrire alle scuole del territorio, e non solo, la possibilità di accedere a un patrimonio culturale che unisce scienza, tecnologia e storia. Un patrimonio davvero unico nel suo genere. L’ambizione è di riuscire a realizzare un contenitore di eventi e di dibattiti che ruotino attorno ai temi più attuali dell’astrofisica, ma che non temono e che anzi cercano forti legami con l’arte tutta, dal teatro alla pittura, dalla musica alla letteratura

The raven’s coloured progressive matrices: norms for Porto Alegre, RS

O Teste das Matrizes Progressivas Coloridas de Raven destina-se à avaliação do desenvolvimento intelectual de crianças de 5 a 11 anos de idade. O presente trabalho teve como objetivo estabelecer normas para as crianças de Porto Alegre – RS. A amostra foi composta por 779 crianças matriculadas em escolas estaduais, de 4 anos e 9 meses a 11 anos e 9 meses. Foi constatado aumento progressivo nas médias de pontos com o aumento da idade e não foram encontradas diferenças entre meninos e meninas. Na comparação com as crianças de escolas públicas de São Paulo, as médias das crianças de Porto Alegre foram mais altas, mas em geral foram inferiores às das escolas particulares de São Paulo. Foram estabelecidas as normas em percentis para cada faixa etária. Os resultados reforçam a necessidade do estabelecimento de normas distintas para as diferentes regiões do Brasil, principalmente em relação aos testes de inteligênciaThe Raven’s Coloured Progressive Matrices was proposed standards to Porto Alegre (RS) children. The sample was composed by 779 children from Porto Alegre state public schools, aged from 4 years and 9 months to 11 years and 9 months. It was found a progressive increase in average scores as age increased and it was not verified differences between boys and girls. Comparing average scores between children from São Paulo and Porto Alegre public schools we found that the average scores from Porto Alegre children was higher, but they were lower than the scores from São Paulo private schools children. Percentile ranks were obtained to each age level with range of six months. Research results show the need to establish specific norms to different Brazilian regions, mainly concerning intelligence test

The raven’s coloured progressive matrices: norms for Porto Alegre, RS

O Teste das Matrizes Progressivas Coloridas de Raven destina-se à avaliação do desenvolvimento intelectual de crianças de 5 a 11 anos de idade. O presente trabalho teve como objetivo estabelecer normas para as crianças de Porto Alegre – RS. A amostra foi composta por 779 crianças matriculadas em escolas estaduais, de 4 anos e 9 meses a 11 anos e 9 meses. Foi constatado aumento progressivo nas médias de pontos com o aumento da idade e não foram encontradas diferenças entre meninos e meninas. Na comparação com as crianças de escolas públicas de São Paulo, as médias das crianças de Porto Alegre foram mais altas, mas em geral foram inferiores às das escolas particulares de São Paulo. Foram estabelecidas as normas em percentis para cada faixa etária. Os resultados reforçam a necessidade do estabelecimento de normas distintas para as diferentes regiões do Brasil, principalmente em relação aos testes de inteligênciaThe Raven’s Coloured Progressive Matrices was proposed standards to Porto Alegre (RS) children. The sample was composed by 779 children from Porto Alegre state public schools, aged from 4 years and 9 months to 11 years and 9 months. It was found a progressive increase in average scores as age increased and it was not verified differences between boys and girls. Comparing average scores between children from São Paulo and Porto Alegre public schools we found that the average scores from Porto Alegre children was higher, but they were lower than the scores from São Paulo private schools children. Percentile ranks were obtained to each age level with range of six months. Research results show the need to establish specific norms to different Brazilian regions, mainly concerning intelligence test

Matrizes progressivas coloridas de Raven - escala especial: normas para Porto Alegre, RS The Raven's coloured progressive matrices: norms for Porto Alegre, RS

O Teste das Matrizes Progressivas Coloridas de Raven destina-se à avaliação do desenvolvimento intelectual de crianças de 5 a 11 anos de idade. O presente trabalho teve como objetivo estabelecer normas para as crianças de Porto Alegre - RS. A amostra foi composta por 779 crianças matriculadas em escolas estaduais, de 4 anos e 9 meses a 11 anos e 9 meses. Foi constatado aumento progressivo nas médias de pontos com o aumento da idade e não foram encontradas diferenças entre meninos e meninas. Na comparação com as crianças de escolas públicas de São Paulo, as médias das crianças de Porto Alegre foram mais altas, mas em geral foram inferiores às das escolas particulares de São Paulo. Foram estabelecidas as normas em percentis para cada faixa etária. Os resultados reforçam a necessidade do estabelecimento de normas distintas para as diferentes regiões do Brasil, principalmente em relação aos testes de inteligência.The Raven's Coloured Progressive Matrices was proposed standards to Porto Alegre (RS) children. The sample was composed by 779 children from Porto Alegre state public schools, aged from 4 years and 9 months to 11 years and 9 months. It was found a progressive increase in average scores as age increased and it was not verified differences between boys and girls. Comparing average scores between children from São Paulo and Porto Alegre public schools we found that the average scores from Porto Alegre children was higher, but they were lower than the scores from São Paulo private schools children. Percentile ranks were obtained to each age level with range of six months. Research results show the need to establish specific norms to different Brazilian regions, mainly concerning intelligence tests

Can apical ballooning cardiomyopathy and anterior STEMI be differentiated based on \u3b21 and \u3b22-adrenergic receptors polymorphisms?

Catecholamine excess along with an exaggerated sympathetic stimulation appears to play a major role in the pathophysiological mechanism of tako-tsubo cardiomyopathy (TTC), which mimics acute ST-elevation myocardial infarction (STEMI). The aim of the present study was to investigate differences in the distribution of allelic variants of \u3b21- and \u3b22-adrenoceptors between TTC and anterior STEMI patients compared to normal subjects

Fibrosis progression in HCV carriers with mild hepatitis who possess the high-repetition variant of the DRD4 gene, a genetic marker for binge-drinking and risk-seeking behavior: a longitudinal study

Alcohol is a major determinant of the outcome of chronic hepatitis C virus (HCV) infection, but self-reported drinking habits lack reliability. We hypothesized that carriage of high-repetition variants (HRV) of the variable number of tandem repeats (VNTR) in exon III of the dopamine receptor D4 gene, linked to binge-drinking and risk-seeking behavior, might be a proxy measure of alcohol consumption, and aimed to verify whether it may affect histologic outcome

Natural course of subclinical hypothyroidism in Down's syndrome: prospective study results and therapeutic considerations.

J Endocrinol Invest 17: 35-40 Pathogenesis, natural course and therapeutic management of subclinical hypothyroidism (SH) in Down's syndrome (DS) remain object of debate in literature. In the present study thyroid function, antithyroid antibody (ATA) prevalence and serum lipid concentrations were investigated in a group of 344 Down patients (DP) and data were compared with those obtained from a control group of 257 age and sex matched healthy subjects. Thyroid function and ATA prevalence were also studied in 120 parents of DP. SH prevalence was clearly higher in DP (32.5% of cases) than in controls (1.1%) and parents (0%). Similarly, ATA prevalence was higher in DP (18% of cases) than in controls (5.8%) and parents (6.6%). In spite of this, no correlation was found in DP between SH and ATA prevalences, since ATA were detected in 18.7% of SH-DP and in 15.8% of euthyroid DP. Thus, circulating ATA were not detected in the majority of SH-DP. No significant differences regarding T4, FT4, T3 and serum lipid levels among SH and euthyroid DP and controls were found. Moreover, TSH levels were only slightly increased, generally less than 10 microU/ml, in most cases of SH-DP. Follow-up was longer than 24 months (range 2-7 years, mean 3.1) in a group of 201 DP: two different patterns of SH course were observed, mainly depending on the presence or the absence of circulating ATA. In particular, 35.7% of ATA-positive SH-DP developed a clinically evident thyroid disease (overt hypothyroidism or hyperthyroidism), while no similar case was recorded among ATA-negative SH-DP.(ABSTRACT TRUNCATED AT 250 WORDS