341 research outputs found

    06N-P63\u3b1 and TA-P63\u3b1 exhibit intrinsic differences in transactivation specificities that depend on distinct features of DNA target sites.

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    TP63 is a member of the TP53 gene family that encodes for up to ten different TA and 06N isoforms through alternative promoter usage and alternative splicing. Besides being a master regulator of gene expression for squamous epithelial proliferation, differentiation and maintenance, P63, through differential expression of its isoforms, plays important roles in tumorigenesis. All P63 isoforms share an immunoglobulin-like folded DNA binding domain responsible for binding to sequence-specific response elements (REs), whose overall consensus sequence is similar to that of the canonical p53 RE. Using a defined assay in yeast, where P63 isoforms and RE sequences are the only variables, and gene expression assays in human cell lines, we demonstrated that human TA- and 06N-P63\u3b1 proteins exhibited differences in transactivation specificity not observed with the corresponding P73 or P53 protein isoforms. These differences 1) were dependent on specific features of the RE sequence, 2) could be related to intrinsic differences in their oligomeric state and cooperative DNA binding, and 3) appeared to be conserved in evolution. Since genotoxic stress can change relative ratio of TA- and 06N-P63\u3b1 protein levels, the different transactivation specificity of each P63 isoform could potentially influence cellular responses to specific stresses

    Prunus persica var. platycarpa (Tabacchiera Peach): bioactive compounds and antioxidant activity of pulp, peel and seed ethanolic extracts

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    A comparative analysis of ethanol extracts from peel, pulp and seed of Prunus persica var. platycarpa (Tabacchiera peach) was done. The total phenols, flavonoids and carotenoids content as well as the antioxidant properties were evaluated. Peach pulp extract was characterized by the highest total phytonutrients content and exhibited the highest antioxidant activity in all in vitro assays. Interestingly, pulp extract showed IC50 values of 2.7 and 2.2 g/mL at 30 and 60 minutes of incubation, respectively using -carotene bleaching test. A remarkable result was also obtained by using Fe-chelating assay (IC50 of 2.9 g/mL vs 1.3 g/mL for positive control BHT). Pulp extract was subjected to liquid chromatography-electrospray-tandem mass spectrometry (HPLC-ESI-MS/MS). Six main compounds, namely gallic acid, protocatechuic acid, protocatechualdehyde, chlorogenic acid, p-coumaric acid, and ferulic acid, were identified. Overall, the results suggest that Prunus persica var. platycarpa displays a good antioxidant activity and its consumption could be promote

    Major scalp defect reconstruction with free flap: analysis of the results

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    Introduction: The purposes of this study were to report 10-years experiences in microsurgical reconstruction of major scalp defects, comparing outcomes, evaluating complications. Materials and methods: From November to July 2015, 10 consecutive patients underwent microsurgical procedures for severe scalp defects. Results: The average age was 55,1 years ranging from 6 to 87 years. The mean follow-up was 16.7 months ranging from 12 to 24 months. The size of the lesions ranged from 9x10 to 16x20cm. The average hospital stay was 20 days ranging from 8 to 43 days. Mean operative times was 5.3 h ranging from 5 to 6.45 h. Free flaps included 8 Latissimus Dorsi flaps (LD) and 2 anterolateral thigh flaps (ALT). The superficial temporal vessels were used as recipient vessels in 9 cases while the superior Thyroid artery was used in remain-ing case. Discussion: For large or complex lesions, the use of free flaps is mandatory. Nowadays LD and ALT flaps are among the most common reconstructive choices for scalp defects reconstructions. Older age does not contraindicate the operation procedure nevertheless in younger patients the size of vessels is proportionately larger and pristine. Conclusion: Microvascular free tissue transfer is the mainstay of scalp defects coverage. In our series early complications are less common and concerning than late complications and in fact reopera-tions are mainly required to manage these latter. Advanced age should be not consider a contraindication for free flap surgery and the procedure can be considered safe and reliable in both old and young population. (www.actabiomedica.it)

    Environmental risk analysis procedure applied to artificial turf sports fields

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    Introduction. Owing to the extensive use of artificial turfs worldwide, over the past ten years there has been much discussion about the possible health and environmental problems originating from Styrene-Butadiene Recycled rubber (SBRr). Materials and methods. In this paper the authors performed a Tier-2 environmental-sanitary risk analysis on five artificial turf sports fields located in the city of Turin (Italy) with the aid of RISC4 software. Two receptors (adult player and child player) and three routes of exposure (direct contact with crumb rubber, contact with rainwater soaking the rubber mat, inhalation of dusts and gases from the artificial turf fields) were considered in the conceptual model. Results and discussion. For all the fields and for all the routes, the cumulative carcinogenic risk proved to be lower than 10-6 and the cumulative non-carcinogenic risk lower than 1. The outdoor inhalation of dusts and gases was the main route of exposure for both carcinogenic and non-carcinogenic substances. The results given by the inhalation pathway were compared with those of a risk assessment carried out on a citizen breathing gases and dusts from traffic emissions every day in Turin. Conclusions. For both classes of substances and for both receptors, the inhalation of atmospheric dusts and gases from vehicular traffic gave risk values of one order of magnitude higher than those due to playing soccer on an artificial fiel

    Radial forearm free flap in a patient with an unusual radial artery variation: a case report

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    Head and neck reconstruction poses unique challenges in rehabilitating surgical defects in terms of integrity, function, and form. The radial forearm free flap (RFFF) has been widely used for defect coverage, especially in the head and neck area, but its versatility allows it to be used for soft-tissue reconstruction in various parts of the body. The vascular features of the flap are quite constant and reliable. Nevertheless, abnormalities of the forearm vascular tree have been described over the decades. We report a case of intraoral reconstruction after verrucous carcinoma recurrence in a 74-year-old woman with an unusual forearm flap, which we called the median forearm free flap, based on a median branch of the radial artery that was preoperatively detected using handheld Doppler ultrasonography. The distally locat-ed skin paddle was predominantly supplied by the aberrant median vessel with its perforators. The flap was thus safely harvested with this atypical pedicle. Successful reconstruction of the intraoral defect was achieved, with an uneventful postoperative course

    PRIMA-1 induces autophagy in cancer cells carrying mutant or wild type p53.

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    PRIMA-1 is a chemical compound identified as a growth suppressor of tumor cells expressing mutant p53. We previously found that in the MDA-MB-231 cell line expressing high level of the mutant p53-R280K protein, PRIMA-1 induced p53 ubiquitination and degradation associated to cell death. In this study, we investigated the ability of PRIMA-1 to induce autophagy in cancer cells. In MDA-MB-231 and HCT116 cells, expressing mutant or wild type p53, respectively, autophagy occurred following exposure to PRIMA-1, as shown by acridine orange staining, anti-LC3 immunofluorescence and immunoblots, as well as by electron microscopy. Autophagy was triggered also in the derivative cell lines knocked-down for p53, although to a different extent than in the parental cells expressing mutant or wild type p53. In particular, while wild type p53 limited PRIMA-1 induced autophagy, mutant p53 conversely promoted autophagy, thus sustaining cell viability following PRIMA-1 treatment. Therefore, the autophagic potential of PRIMA-1, besides being cell context dependent, could be modulated in a different way by the presence of wild type or mutant p53. Furthermore, since both cell lines lacking p53 were more sensitive to the cytotoxic effect of PRIMA-1 than the parental ones, our findings suggest that a deregulated autophagy may favor cell death induced by this drug

    Induction of Labor According to Medical Indications: A Critical Evaluation through a Prospective Study

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    Background: The induction of labor (IOL) is a common obstetric intervention, steadily increasing (one out four pregnancies) in the last years. This procedure should be considered only when there is a medical indication, and when the benefits outweigh the maternal and/or fetal risks of waiting for spontaneous onset of labor. Therefore, this study aims to compare the efficacy of the IOL in terms of induction to delivery time, mode of delivery, and neonatal well-being among different evidence-based and non-evidence-based indications. Methods: This prospective study was conducted at the University Hospital of Modena, between January and December 2020. We included singleton pregnant women undergoing IOL, at the term. Intrauterine deaths, small for gestational age fetuses <5th centile as well women with hypertensive disorders were excluded. Women have been subdivided into 3 groups based on the indication to IOL: premature rupture of membranes (PROM), post-date pregnancy (>41 weeks + 3 days), and non-evidence-based indications (NEBI). The primary outcome is the time occurring between IOL and delivery (TIME), analyzing separately by parity. Moreover, mode of delivery and neonatal wellbeing were evaluated. Results: A total of 585 women underwent IOL in the study period. Overall, the median TIME between IOL and delivery was 19 hours, and the mean cesarean section CS rate was 15.5% (91/585). Pregnancies induced for postdate and non-evidencebased indications registered respectively a significantly higher mean time (p < 0.001), compared with women induced for PROM. This occurred both in nulliparous and multiparous women. Moreover, at multivariate analysis, the IOL TIME ≥24 hours was significantly influenced by Bishop score (p = 0.000) and NEBI (p = 0.02) in nulliparous and by gestational age (p = 0.000) and NEBI (p = 0.02) in multiparous. Moreover, CS rate was significantly influenced by Bishop score (p = 0.003) in nulliparous and by gestational age (p = 0.01) in multiparous. Finally, neonatal intensive care unit (NICU) admission resulted significantly influenced only by gestational age (p = 0.002) in multiparous. Conclusions: Our study confirms that IOL in non-evidence-based indications, leads to an increase in induction to delivery time comparing with women induced for PROM, both in nulliparous and multiparous women, thus it should be justified and carefully evaluated. Further randomized controlled trials (RCT) conducted in European/Italian settings are needed to determine the perinatal outcomes of IOL in non-evidence-based indications
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