Antiretroviral treatment efficacy after mutations reversion during T20 monotherapy, an alternative strategy in multi-failed HIV-1 infected patients

Purpose of the study Monotherapy maintenance with 3TC after multiple therapeutic failure, helps in maintaining the number of CD4, but, at the same time, slows down the speed of reversion of mutations usually achieved during complete interruption of therapy. Monotherapy with enfuvirtide (T20) can be an interesting alternative to 3TC monotherapy, due to the CD4-enhancement typical of this drug even during therapeutic failure. Aim of this study was to assess, in a proof-of-concept study, the efficacy of T20-monotherapy to maintain the levels of CD4, to allow reversal of mutations in the pol gene, and eventually to favor long-term success of subsequent HAART

Case report: Preemptive intervention for an infant with early signs of autism spectrum disorder during the first year of life

Autism spectrum disorder (ASD) includes neurodevelopmental conditions traditionally considered to bring life long disabilities, severely impacting individuals and their families. Very early identification and intervention during the very first phases of life have shown to significantly diminish symptom severity and disability, and improve developmental trajectories. Here we report the case of a young child showing early behavioral signs of ASD during the first months of life, including diminished eye contact, reduced social reciprocity, repetitive movements. The child received a pre-emptive parent mediated intervention based on the Infant Start, an adaptation of the Early Start Denver Model (ESDM), specifically developed for children with ASD signs during the first year of life. The child here described received intervention from 6 to 32 months of age, in combination with educational services. Diagnostic evaluations performed at several time points (8, 14, 19, and 32 months) showed progressive improvements in his developmental level and ASD symptoms. Our case study supports the possibility of identifying ASD symptoms and providing services as soon as concerns emerge even during the first year of life. Our report, in combination with recent infant identification and intervention studies, suggests the need for very early screening and preemptive intervention to promote optimal outcomes

Analisar a Materialidade no Cinema Português: Estéticas e práticas

UIDB/04209/2020 UIDP/04209/2020Texto de introdução ao dossier temático da autoria dos editores convidados Caterina Cucinotta e Federico Pierotti. Os autores situam o seu contributo no quadro do materialist turn que se tem feito sentir, em várias disciplinas, nos últimos vinte anos, para propor uma abordagem ao cinema português que dedica particular atenção aos conceitos de materialidade, estética fílmica e práticas cinematográficas. Os cinco ensaios do dossier são apresentados à luz dos três tipos de materialidade identificados pelo arqueólogo dos média Jussi Parikka: a materialidade da prática cultural; a materialidade dos materiais; e a materialidade da tecnologia. O resultado é um programa fértil que promete assegurar o futuro dos estudos da materialidade no cinema português.publishersversionpublishe

Metformin as an Adjuvant Drug against Pediatric Sarcomas: Hypoxia Limits Therapeutic Effects of the Drug

Metformin, a well-known insulin-sensitizer commonly used for type 2 diabetes therapy, has recently emerged as potentially very attractive drug also in oncology. It is cheap, it is relatively safe and many reports have indicated effects in cancer prevention and therapy. These desirable features are particularly interesting for pediatric sarcomas, a group of rare tumors that have been shown to be dependent on IGF and insulin system for pathogenesis and progression. Metformin exerts anti-mitogenic activity in several cancer histotypes through several molecular mechanisms. In this paper, we analyzed its effects against osteosarcoma, Ewing sarcoma and rhabdomyosarcoma, the three most common pediatric sarcomas. Despite in vitro metformin gave remarkable antiproliferative and chemosensitizing effects both in sensitive and chemoresistant cells, its efficacy was not confirmed against Ewing sarcoma xenografts neither as single agent nor in combination with vincristine. This discrepancy between in vitro and in vivo effects may be due to hypoxia, a common feature of solid tumors. We provide evidences that in hypoxia conditions metformin was not able to activate AMPK and inhibit mTOR signaling, which likely prevents the inhibitory effects of metformin on tumor growth. Thus, although metformin may be considered a useful complement of conventional chemotherapy in normoxia, its therapeutic value in highly hypoxic tumors may be more limited. The impact of hypoxia should be considered when novel therapies are planned for pediatric sarcomas

Trends in chronic hepatitis B virus infection in Italy over a 10-year period: Clues from the nationwide PITER and MASTER cohorts toward elimination

Objectives: The study measures trends in the profile of patients with chronic hepatitis B virus linked to care in Italy. Methods: A cross-sectional, multicenter, observational cohort (PITER cohort) of consecutive patients with hepatitis B surface antigen (HBsAg) over the period 2019-2021 from 46 centers was evaluated. The reference was the MASTER cohort collected over the years 2012-2015. Standard statistical methods were used. Results: The PITER cohort enrolled 4583 patients, of whom 21.8% were non-Italian natives. Compared with those in MASTER, the patients were older and more often female. The prevalence of hepatitis B e antigen (HBeAg) declined (7.2% vs 12.3; P <0.0001) and that of anti-hepatitis D virus (HDV) remained stable (9.3% vs 8.3%). In both cohorts, about 25% of the patients had cirrhosis, and those in the PITER cohort were older. HBeAg-positive was 5.0% vs 12.6% (P <0.0001) and anti-HDV positive 24.8% vs 17.5% (P <0.0017). In the logistic model, the variables associated with cirrhosis were anti-HDV-positive (odds ratio = 10.08; confidence interval 7.63-13.43), age, sex, and body mass index; the likelihood of cirrhosis was reduced by 40% in the PITER cohort. Among non-Italians, 12.3% were HBeAg-positive (vs 23.4% in the MASTER cohort; P <0.0001), and 12.3% were anti-HDV-positive (vs 11.1%). Overall, the adherence to the European Association for the Study of the Liver recommendations for antiviral treatment increased over time. Conclusion: Chronic hepatitis B virus infection appears to be in the process of becoming under control in Italy; however, HDV infection is still a health concern in patients with cirrhosis and in migrants

FANCM c.5791C > T nonsense mutation (rs144567652) induces exon skipping, affects DNA repair activity and is a familial breast cancer risk factor

Numerous genetic factors that influence breast cancer risk are known. However, approximately two-thirds of the overall familial risk remain unexplained. To determine whether some of the missing heritability is due to rare variants conferring high to moderate risk, we tested for an association between the c.5791C>T nonsense mutation (p.Arg1931*; rs144567652) in exon 22 of FANCM gene and breast cancer. An analysis of genotyping data from 8635 familial breast cancer cases and 6625 controls from different countries yielded an association between the c.5791C>T mutation and breast cancer risk [ odds ratio (OR) = 3.93 (95% confidence interval (CI) = 1.28-12.11; P = 0.017)]. Moreover, we performed two meta-analyses of studies from countries with carriers in both cases and controls and of all available data. These analyses showed breast cancer associations with OR = 3.67 (95% CI = 1.04-12.87; P = 0.043) and OR = 3.33 (95% CI = 1.09-13.62; P = 0.032), respectively. Based on information theory-based prediction, we established that the mutation caused an out-of-frame deletion of exon 22, due to the creation of a binding site for the pre-mRNA processing protein hnRNP A1. Furthermore, genetic complementation analyses showed that the mutation influenced the DNA repair activity of the FANCM protein. In summary, we provide evidence for the first time showing that the common p.Arg1931* loss-of-function variant in FANCM is a risk factor for familial breast cancer