678 research outputs found

    Iterative algorithms for a non-linear inverse problem in atmospheric lidar

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    We consider the inverse problem of retrieving aerosol extinction coefficients from Raman lidar measurements. In this problem the unknown and the data are related through the exponential of a linear operator, the unknown is non-negative and the data follow the Poisson distribution. Standard methods work on the log-transformed data and solve the resulting linear inverse problem, but neglect to take into account the noise statistics. In this study we show that proper modelling of the noise distribution can improve substantially the quality of the reconstructed extinction profiles. To achieve this goal, we consider the non-linear inverse problem with non-negativity constraint, and propose two iterative algorithms derived using the Karush-Kuhn-Tucker conditions. We validate the algorithms with synthetic and experimental data. As expected, the proposed algorithms outperform standard methods in terms of sensitivity to noise and reliability of the estimated profile.Comment: 19 pages, 6 figure

    Functional health literacy of asylum seekers and refugees. A pilot study in italy

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    Literature shows how some groups of populations, among which are people seeking international protection and refugees, find it difficult to access services in national health systems. Usually, asylum seekers have limited Health Literacy (HL), which makes understanding the appropriate health information difficult. The objective of this research is to consider the relationship between how people requesting international protection and refugees approach the Italian Health System to request health services and their level of Functional Health Literacy (FHL). These relationships are examined through mixed methods. Data were obtained using several tools: a self-administered questionnaire in which the subjects revealed social and demographic data and a face-to-face interview together with the S-FHL Scale fulfilment in order to identify the functional level of HL. Twenty-one subjects were interviewed in two Centers of Protection System for Asylum Seekers and Refugees (SPRAR). Results show a picture of the actual situation. Data report a problematic or insufficient FHL level. Some factors, such as gender, age and health perceptions, play a role in the FHL levels. Some racial prejudices were reported. Language barriers had the most impact on the communication gap. Nevertheless, none of the subjects were denied health services. In conclusion, although this study is a pilot, we have experienced difficulty in obtaining asylum seekers’ trust to be open about their experience. This explains the number of the sample that should be more indicated for a qualitative study. Our results are in accordance with literature for inadequate level of FHL and lack of knowledge of the Italian Health System. This study highlighted several other issues to be taken into consideration for future research on the subject

    The importance of glial cells in the homeostasis of the retinal microenvironment and their pivotal role in the course of diabetic retinopathy

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    Abstract Diabetic retinopathy (DR) is a remarkable microvascular complication of diabetes and it has been considered the leading cause of legal blindness in working-age adults in the world. Several overlapping and interrelated molecular pathways are involved in the development of this disease. DR is staged into different levels of severity, from the nonproliferative to the advanced proliferative form. Over the years the progression of DR evolves through a series of changes involving distinct types of specialized cells: neural, vascular and glial. Prior to the clinically observable vascular complications, hyperglycemia and inflammation affect retinal glial cells which undergo a wide range of structural and functional alterations. In this review, we provide an overview of the status of macroglia and microglia in the course of DR, trying to briefly take into account the complex biochemical mechanisms that affect the intimate relationship among neuroretina, vessels and glial cells

    5-FU targets rpL3 to induce mitochondrial apoptosis via cystathionine-b-synthase in colon cancer cells lacking p53

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    Recent findings revealed in cancer cells novel stress response pathways, which in response to many chemotherapeutic drugs causing nucleolar stress, will function independently from tumor protein p53 (p53) and still lead to cell cycle arrest and/or apoptosis. Since it is known that most cancers lack functional p53, it is of great interest to explore these emerging molecular mechanisms. Here, we demonstrate that nucleolar stress induced by 5-fluorouracil (5-FU) in colon cancer cells devoid of p53 leads to the activation of ribosomal protein L3 (rpL3) as proapoptotic factor. rpL3, as ribosome-free form, is a negative regulator of cystathionine-β-synthase (CBS) expression at transcriptional level through a molecular mechanism involving Sp1. The rpL3-CBS association affects CBS stability and, in addition, can trigger CBS translocation into mitochondria. Consequently apoptosis will be induced through the mitochondrial apoptotic cell death pathway characterized by an increased ratio of Bax to Bcl-2, cytochrome c release and subsequent caspase activation. It is noteworthy that silencing of CBS is associated to a strong increase of 5-FU-mediated inhibition of cell migration and proliferation. These data reveal a novel mechanism to accomplish p53-independent apoptosis and suggest a potential therapeutic approach aimed at upregulating rpL3 for treating cancers lacking p53

    A night of sleep deprivation alters brain connectivity and affects specific executive functions

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    : Sleep is a fundamental physiological process necessary for efficient cognitive functioning especially in relation to memory consolidation and executive functions, such as attentional and switching abilities. The lack of sleep strongly alters the connectivity of some resting-state networks, such as default mode network and attentional network. In this study, by means of magnetoencephalography (MEG) and specific cognitive tasks, we investigated how brain topology and cognitive functioning are affected by 24 h of sleep deprivation (SD). Thirty-two young men underwent resting-state MEG recording and evaluated in letter cancellation task (LCT) and task switching (TS) before and after SD. Results showed a worsening in the accuracy and speed of execution in the LCT and a reduction of reaction times in the TS, evidencing thus a worsening of attentional but not of switching abilities. Moreover, we observed that 24 h of SD induced large-scale rearrangements in the functional network. These findings evidence that 24 h of SD is able to alter brain connectivity and selectively affects cognitive domains which are under the control of different brain networks

    Human Cystathionine-β-Synthase Phosphorylation on Serine227 Modulates Hydrogen Sulfide Production in Human Urothelium

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    Urothelium, the epithelial lining the inner surface of human bladder, plays a key role in bladder physiology and pathology. It responds to chemical, mechanical and thermal stimuli by releasing several factors and mediators. Recently it has been shown that hydrogen sulfide contributes to human bladder homeostasis. Hydrogen sulfide is mainly produced in human bladder by the action of cystathionine-β-synthase. Here, we demonstrate that human cystathionine-β-synthase activity is regulated in a cGMP/PKG-dependent manner through phosphorylation at serine 227. Incubation of human urothelium or T24 cell line with 8-Bromo-cyclic-guanosine monophosphate (8-Br-cGMP) but not dibutyryl-cyclic-adenosine monophosphate (d-cAMP) causes an increase in hydrogen sulfide production. This result is congruous with the finding that PKG is robustly expressed but PKA only weakly present in human urothelium as well as in T24 cells. The cGMP/PKG-dependent phosphorylation elicited by 8-Br-cGMP is selectively reverted by KT5823, a specific PKG inhibitor. Moreover, the silencing of cystathionine-β-synthase in T24 cells leads to a marked decrease in hydrogen sulfide production either in basal condition or following 8-Br-cGMP challenge. In order to identify the phosphorylation site, recombinant mutant proteins of cystathionine-β-synthase in which Ser32, Ser227 or Ser525 was mutated in Ala were generated. The Ser227Ala mutant cystathionine-β-synthase shows a notable reduction in basal biosynthesis of hydrogen sulfide becoming unresponsive to the 8-Br-cGMP challenge. A specific antibody that recognizes the phosphorylated form of cystathionine-β-synthase has been produced and validated by using T24 cells and human urothelium. In conclusion, human cystathionine-β-synthase can be phosphorylated in a PKG-dependent manner at Ser227 leading to an increased catalytic activity

    Urothelium muscarinic activation phosphorylates CBS Ser227 via cGMP/PKG pathway causing human bladder relaxation through H 2 S production

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    The urothelium modulates detrusor activity through releasing factors whose nature has not been clearly defined. Here we have investigated the involvement of H2S as possible mediator released downstream following muscarinic (M) activation, by using human bladder and urothelial T24 cell line. Carbachol stimulation enhances H2S production and in turn cGMP in human urothelium or in T24 cells. This effect is reversed by cysthationine-β-synthase (CBS) inhibition. The blockade of M1 and M3 receptors reverses the increase in H2S production in human urothelium. In T24 cells, the blockade of M1 receptor significantly reduces carbachol-induced H2S production. In the functional studies, the urothelium removal from human bladder strips leads to an increase in carbachol-induced contraction that is mimicked by CBS inhibition. Instead, the CSE blockade does not significantly affect carbachol-induced contraction. The increase in H2S production and in turn of cGMP is driven by CBS-cGMP/PKG-dependent phosphorylation at Ser(227) following carbachol stimulation. The finding of the presence of this crosstalk between the cGMP/PKG and H2S pathway downstream to the M1/M3 receptor in the human urothelium further implies a key role for H2S in bladder physiopathology. Thus, the modulation of the H2S pathway can represent a feasible therapeutic target to develop drugs for bladder disorders

    Contribution of miR-145-5p/Ago2 complex to the regulation of epithelial-mesenchymal transition

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    The epithelial-mesenchymal transition (EMT) is essential for cell fate determination during development but it is involved in pathological processes like cancer as well, being one of the first steps in the mechanisms leading to metastasis. miR-145-5p is one of the most widely recognized tumor-suppressor miRNAs, able to regulate cell migration and EMT through the contribution of the RISC complex in which Argonaute (Ago) proteins are required for target recognition and gene silencing [1]. Ago2 is an important member of the Ago family and its overexpression correlates with a transformed phenotype in breast cancer cells [2]. With the aim to unravel miR-145-5p/Ago2 contribution to the suppression of cancer progression in epithelial tumors, here we show that: i) miR-145-5p and Ago2 are down-regulated in breast tumor vs normal tissues; ii) the restored expression of miR-145-5p in breast cancer cell lines results in the reduction of tumor phenotype; iii) Ago2 expression is positively and specifically regulated by miR-145-5p; iv) miR-145-5p-dependent Ago2 induction is necessary for the inhibition of cell migration; v) when Ago2 is depleted, the formation of an alternative miR-145-5p/Ago1 active complex redirects miR-145-5p tumor suppressor function and correlates with a more invasive phenotype in breast cancer cells. These results open to the identification of miR-145-5p/Ago2-dependent molecular networks involved in the maintenance and progression of cancer phenotype

    Scar-Free Laparoscopy in BRCA-Mutated Women

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    Background and Objectives: BRCA 1 and 2 mutations have a cumulative risk of developing ovarian cancer at 70 years of 41% and 15%, respectively, while a cumulative risk of breast cancer by 80 years of age was 72% for BRCA1 mutation carriers and 69% for BRCA2 mutation carriers. The NCCN recommends risk-reducing salpingo-oophorectomy (RRSO), typically between 35 and 40 years, and upon completion of childbearing in BRCA1 mutation, while it is reasonable to delay RRSO for management of ovarian cancer risk until age 40–45 years in patients with BRCA2. In recent years there have been two main lines of evolution in laparoscopy. The former concerning the development of a single-site laparoscopic and the latter concerning the miniaturisation of laparoscopic instruments (mini/micro-laparoscopy). Materials and Methods: In this case report, we show our experience in prophylactic adnexectomy, on a mutated-BRCA patient, using the MiniLap® percutaneous surgical system. Results: This type of technique is safe and effective and does not require a particular learning curve compared to single-port laparoscopy. Conclusions: The considerable aesthetic advantage of the scars, we believe, albeit to a lesser extent, is useful to find in these patients burdened by an important stress loa

    The PI3K/AKT pathway is activated by HGF in NT2D1 non-seminoma cells and has a role in the modulation of their malignant behavior

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    Overactivation of the c-MET/HGF system is a feature of many cancers. We previously reported that type II testicular germ cell tumor (TGCT) cells express the c-MET receptor, forming non-seminomatous lesions that are more positive compared with seminomatous ones. Notably, we also demonstrated that NT2D1 non-seminomatous cells (derived from an embryonal carcinoma lesion) increase their proliferation, migration, and invasion in response to HGF. Herein, we report that HGF immunoreactivity is more evident in the microenvironment of embryonal carcinoma biopsies with respect to seminomatous ones, indicating a tumor-dependent modulation of the testicular niche. PI3K/AKT is one of the signaling pathways triggered by HGF through the c-MET activation cascade. Herein, we demonstrated that phospho-AKT increases in NT2D1 cells after HGF stimulation. Moreover, we found that this pathway is involved in HGF-dependent NT2D1 cell proliferation, migration, and invasion, since the co-administration of the PI3K inhibitor LY294002 together with HGF abrogates these responses. Notably, the inhibition of endogenous PI3K affects collective cell migration but does not influence proliferation or chemotactic activity. Surprisingly, LY294002 administered without the co-administration of HGF increases cell invasion at levels comparable to the HGF-administered samples. This paradoxical result highlights the role of the testicular microenvironment in the modulation of cellular responses and stimulates the study of the testicular secretome in cancer lesions
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