1,906 research outputs found

    Vitamin A, cancer treatment and prevention: The new role of cellular retinol binding proteins

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    Retinol and vitamin A derivatives influence cell differentiation, proliferation, and apoptosis and play an important physiologic role in a wide range of biological processes. Retinol is obtained from foods of animal origin. Retinol derivatives are fundamental for vision, while retinoic acid is essential for skin and bone growth. Intracellular retinoid bioavailability is regulated by the presence of specific cytoplasmic retinol and retinoic acid binding proteins (CRBPs and CRABPs). CRBP-1, the most diffuse CRBP isoform, is a small 15 KDa cytosolic protein widely expressed and evolutionarily conserved in many tissues. CRBP-1 acts as chaperone and regulates the uptake, subsequent esterification, and bioavailability of retinol. CRBP-1 plays a major role in wound healing and arterial tissue remodelling processes. In the last years, the role of CRBP-1-related retinoid signalling during cancer progression became object of several studies. CRBP-1 downregulation associates with a more malignant phenotype in breast, ovarian, and nasopharyngeal cancers. Reexpression of CRBP-1 increased retinol sensitivity and reduced viability of ovarian cancer cells in vitro. Further studies are needed to explore new therapeutic strategies aimed at restoring CRBP-1-mediated intracellular retinol trafficking and the meaning of CRBP-1 expression in cancer patients' screening for a more personalized and efficacy retinoid therapy

    Long‐term follow‐up comparison of two different bi‐layer dermal substitutes in tissue regeneration: Clinical outcomes and histological findings

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    Double layer dermal substitute (DS) consist of a 3-dimensional collagen structures and a superficial silicon layer that are positioned within the defect provide to promote tissue regeneration in skin wounds. DS often have unique physical characteristics due to differences in manufacturing techniques. The aim of this study is the clinical and histological comparison of Nevelia and Integra double layer DSs in patients with post-traumatic injury wounds. Thirty patients with post-traumatic wounds localised on the inferior limbs were randomised in 2 groups Nevelia or Integra, followed by autologous dermal epidermal graft (DEG). Clinical results were evaluated through the healing time; Manchester Scar Scale (MSS) and Visual Analog Scale (VAS) at 1, 2, and 3 weeks and after 1 and 3 years. Histological and immunohistochemical evaluation were performed at 0, 2, and 3 weeks. The difference in healing time between groups (P = .467, log-rank test), pain and self-estimation was not statistically significant after 35, 42, and 49 days and at 1-year follow up. Histological data showed evident healing of wound after 2 weeks compared with preoperative with both DSs. At 3 weeks reepithelialisation and dermal regeneration were evident with both substitutes; however Nevelia showed early regenerative properties in terms of epidermal proliferation and dermal renewal compared with Integra. Nevelia showed also a more evident angiogenesis vs Integra evaluated as α-SMA immunohistochemistry. Differences in the MSS score were statistically significant at 3 years follow up in favour of Nevelia group (P = .001). At long-term follow up, Nevelia showed a better clinical outcome measured as MSS score vs Integra measured as MSS. Histological and immunohistochemistry data showed that Nevelia allows faster neoangiogenesis and tissue regeneration with neoformed tissue architecture closer to the physiology of the skin

    Biomechanical properties and histomorphometric features of aortic tissue in patients with or without bicuspid aortic valve

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    Background: We sought to investigate and compare biomechanical properties and histomorphometric findings of thoracic ascending aorta aneurysm (TAA) tissue from patients with bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV) in order to clarify mechanisms underlying differences in the clinical course. Methods: Circumferential sections of TAA tissue in patients with BAV (BAV-TAA) and TAV (TAV-TAA) were obtained during surgery and used for biomechanical tests and histomorphometrical analysis. Results: In BAV-TAA, we observed biomechanical higher peak stress and lower Young modulus values compared with TAV-TAA wall. The right lateral longitudinal region seemed to be the most fragile zone of the TAA wall. Mechanical stress-induced rupture of BAV-TAA tissue was sudden and uniform in all aortic wall layers, whereas a gradual and progressive aortic wall breakage was described in TAV-TAA. Histomorphometric analysis revealed higher amount of collagen but not elastin in BAV-TAA tunica media. Conclusions: The higher deformability of BAV-TAA tissue supports the hypothesis that increased wall shear stress doesn't explain the increased risk of sudden onset of rupture and dissection; other mechanisms, likely related to alteration of specific genetic pathways and epigenetic signals, could be investigated to explain differences in aortic dissection and rupture in BAV patients

    A new Low Gain Avalanche Diode concept: the double-LGAD

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    This paper describes the new concept of the double-LGAD. The goal is to increase the charge at the input of the electronics, keeping a time resolution equal or better than a standard (single) LGAD; this has been realized by adding the charges of two coupled LGADs while still using a single front-end electronics. The study here reported has been done starting from single LGAD with a thickness of 25 \textmu{m}, 35 \textmu{m} and 50 \textmu{m}.Comment: arXiv admin note: text overlap with arXiv:2208.0571

    INFN What Next: Ultra-relativistic Heavy-Ion Collisions

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    This document was prepared by the community that is active in Italy, within INFN (Istituto Nazionale di Fisica Nucleare), in the field of ultra-relativistic heavy-ion collisions. The experimental study of the phase diagram of strongly-interacting matter and of the Quark-Gluon Plasma (QGP) deconfined state will proceed, in the next 10-15 years, along two directions: the high-energy regime at RHIC and at the LHC, and the low-energy regime at FAIR, NICA, SPS and RHIC. The Italian community is strongly involved in the present and future programme of the ALICE experiment, the upgrade of which will open, in the 2020s, a new phase of high-precision characterisation of the QGP properties at the LHC. As a complement of this main activity, there is a growing interest in a possible future experiment at the SPS, which would target the search for the onset of deconfinement using dimuon measurements. On a longer timescale, the community looks with interest at the ongoing studies and discussions on a possible fixed-target programme using the LHC ion beams and on the Future Circular Collider.Comment: 99 pages, 56 figure

    Silver sulfadiazine eradicates antibiotic-tolerant Staphylococcus aureus and Pseudomonas aeruginosa biofilms in patients with infected diabetic foot ulcers

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    Infections are among the most frequent and challenging events in diabetic foot ulcers (DFUs). Pathogenic bacteria growing in biofilms within host tissue are highly tolerant to environmental and chemical agents, including antibiotics. The present study was aimed at assessing the use of silver sulfadiazine (SSD) for wound healing and infection control in 16 patients with DFUs harboring biofilm-growing Staphylococcus aureus and Pseudomonas aeruginosa. All patients received a treatment based on a dressing protocol including disinfection, cleansing, application of SSD, and application of nonadherent gauze, followed by sterile gauze and tibio-breech bandage, in preparation for toilet surgery after 30 days of treatment. Clinical parameters were analyzed by the T.I.M.E. classification system. In addition, the activity of SSD against biofilm-growing S. aureus and P. aeruginosa isolates was assessed in vitro. A total of 16 patients with S. aureus and P. aeruginosa infected DFUs were included in the study. Clinical data showed a statistically significant (p < 0.002) improvement of patients’ DFUs after 30 days of treatment with SSD with significant amelioration of all the parameters analyzed. Notably, after 30 days of treatment, resolution of infection was observed in all DFUs. In vitro analysis showed that both S. aureus and P. aeruginosa isolates developed complex and highly structured biofilms. Antibiotic susceptibility profiles indicated that biofilm cultures were significantly (p ≤ 0.002) more tolerant to all tested antimicrobials than their planktonic counterparts. However, SSD was found to be effective against fully developed biofilms of both S. aureus and P. aeruginosa at concentrations below those normally used in clinical preparations (10 mg/mL). These results strongly suggest that the topical administration of SSD may represent an effective alternative to conventional antibiotics for the successful treatment of DFUs infected by biofilm-growing S. aureus and P. aeruginosa

    Multiplicity Studies and Effective Energy in ALICE at the LHC

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    In this work we explore the possibility to perform ``effective energy'' studies in very high energy collisions at the CERN Large Hadron Collider (LHC). In particular, we focus on the possibility to measure in pppp collisions the average charged multiplicity as a function of the effective energy with the ALICE experiment, using its capability to measure the energy of the leading baryons with the Zero Degree Calorimeters. Analyses of this kind have been done at lower centre--of--mass energies and have shown that, once the appropriate kinematic variables are chosen, particle production is characterized by universal properties: no matter the nature of the interacting particles, the final states have identical features. Assuming that this universality picture can be extended to {\it ion--ion} collisions, as suggested by recent results from RHIC experiments, a novel approach based on the scaling hypothesis for limiting fragmentation has been used to derive the expected charged event multiplicity in AAAA interactions at LHC. This leads to scenarios where the multiplicity is significantly lower compared to most of the predictions from the models currently used to describe high energy AAAA collisions. A mean charged multiplicity of about 1000-2000 per rapidity unit (at η0\eta \sim 0) is expected for the most central PbPbPb-Pb collisions at sNN=5.5TeV\sqrt{s_{NN}} = 5.5 TeV.Comment: 12 pages, 19 figures. In memory of A. Smirnitski

    Measurements of the Cherenkov effect in direct detection of charged particles with SiPMs

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    In this paper, different Silicon PhotoMultiplier (SiPM) sensors have been tested with charged particles to characterize the Cherenkov light produced in the sensor protection layer. A careful position scan of the SiPM response has been performed with different prototypes, confirming the large number of firing cells and proving almost full efficiency, with the SiPM filling factor essentially negligible. This study also allowed us to study the time resolution of such devices as a function of the number of firing cells, reaching values below 20 ps. These measurements provide significant insight into the capabilities of SiPM sensors in direct detection of charged particles and their potential for several applications

    Direct detection of charged particles with SiPMs

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    The direct response of Silicon PhotoMultipliers being traversed by a MIP charged particle have been studied in a systematic way for the first time. Using beam test data, time resolution and the crosstalk probability have been measured. A characterization of the SiPM by means of a laser beam is also reported. The results obtained for different sensors indicate a measured time resolution around 40-70 ps. Although particles are expected to traverse only one SPAD per event, crosstalk measurements on different sensors indicate an unexpected higher value with respect to the one related to the sensor noise
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