2176 research outputs found
Sort by
Lo sguardo trasversale per un approccio integrato: l'utilizzo del Formetric nel trattamento di pazienti affetti da Sclerosi Multipla
No full textChromatography and mass spectrometry in the study of structure and dynamics of chiral molecules
No full textPart A
Dynamic high performance liquid chromatography on chiral stationary phases is a consolidated technique that allows the investigation of chiral molecules with labile stereogenic elements that interconvert very quickly at room temperature and result in stereoinversion processes occurring on the time scale of the separation process. Kinetic parameters for on-column interconversions can be extracted from exchange-deformed experimental peak profiles by computer simulation. The technique has been used in a wide range of temperatures and is complementary in scope to dynamic nuclear magnetic resonance spectroscopy.
Here we report, in the first part, the separation of the enantiomers of benzodiazepines, a class of molecules whose conformational enantiomers interconvert not only through a single bond rotation but also via “ring-flip” inversion. The second part concerns the first HPLC resolution of the conformational enantiomers of tri-O-thymotide (TOT) a
macrocyclic trilactone existing in fast-exchanging multiple chiral conformations. Variable chromatography on brush type stationary phases showed dynamic features due to on-column interconversions of TOT.
Part B
Chiral recognition is a branch of chemistry aimed at understanding the reactivity as well as the size- and shape-specificity of non-covalent interactions between molecular aggregates formed by chiral species. Mass spectrometry (MS) is a powerful tool for investigating chiral recognition in the gas phase in the absence of perturbing environmental phenomena and discriminating and even quantifying chiral species by interaction with chiral reference molecules.
A small library of synthetic receptors was prepared by macrocyclization of complementary A and B fragments to yield A2B2 macrocycles, where A are activated forms of isophthalic acid derivatives and B are chiral, C2 symmetric 1,2-diamines derived from 1,2-diphenylethylendiamine. Their enantioselectivity was investigated by ESI-MS and revealed large enantioselectivities towards the enantiomers of aminoacids and peptide guests. The stability of the complexes increases with the size of guests and with large aromatic portions on the guest.
Part C
This part of my academic program was developed at the University of California, Davis, under the supervision of prof. Carlito Lebrilla, during the last period of my Ph.D. activity.
An important goal in proteomic is to quantify the profile changes of protein abundances in biological systems. Quantifying these changes is a key to understand changes in cell state at a molecular level.
In the last years label-free quantitation using MRM (multiple reaction monitoring), which correlates the mass spectrometric signal of intact proteolytic peptides with the relative or absolute protein quantity, is become a powerful tool for accurate quantitation. Here we report a label-free method to quantify proteins and their glycoforms in biologic fluids (milk, feces and urine) by MRM, including the selection of proteotryptic peptides and the optimization and validation of transitions
The role of PET18 F-FDOPA in the evaluation of low grade gliomas.
No full text1) Low grade gliomas are in general relatively slow-growing brain tumor, but they have a very heterogeneous clinical and biomolecular behavior.
2) The optimal treatment of low grade glioma remains controversial, i.e “wait-and-see” versus treatment.
3) The MRI is considered the gold standard in the evaluation of low grade glioma, but has several limitations. Since the glioma growth does not obey an exponential evolution due to the diffusion of many newly produced tumor cells into the surrounding parenchyma. Therefore, the tumor density does not reach the minimal threshold required to appear on MRI.
4) The PET 18 F-FDOPA has good sensitivity and specificity in the evaluation of brain tumor recurrence, mainly in the evaluation of the recurrence of low grade or high grade malignant gliomas.
5) In our study, PET 18 F-FDOPA demonstrated not a potential diagnostic role, but also a prognostic value in predicting progression of disease
The effects of cannabidiol and its synergism with bortezomib in multiple myeloma cell lines. A role for transient receptor potential vanilloid type-2
No full textMultiple myeloma (MM) is a plasma cell (PC) malignancy characterised by the accumulation of a monoclonal PC population in the bone marrow (BM). Cannabidiol (CBD) is a non-psychoactive cannabinoid with antitumoural activities, and the transient receptor potential vanilloid type-2 (TRPV2) channel has been reported as a potential CBD receptor. TRPV2 activation by CBD decreases proliferation and increases susceptibility to drug-induced cell death in human cancer cells. However, no functional role has been ascribed to CBD and TRPV2 in MM. In this study, we identified the presence of heterogeneous CD138+TRPV2+ and CD138+TRPV2- PC populations in MM patients, whereas only the CD138+ TRPV2- population was present in RPMI8226 and U266 MM cell lines. Because bortezomib (BORT) is commonly used in MM treatment, we investigated the effects of CBD and BORT in CD138+TRPV2- MM cells and in MM cell lines transfected with TRPV2 (CD138+TRPV2+). These results showed that CBD by itself or in synergy with BORT strongly inhibited growth, arrested cell cycle progression and induced MM cells death by regulating the ERK, AKT and NF-κB pathways with major effects in TRPV2+ cells. These data provide a rationale for using CBD to increase the activity of proteasome inhibitors in MM
Identification and characterization of three novel LytM proteins of non-typeable Haemophilus influenzae involved in cell division, Outer Membrane Vesicles production and pathogenesis
No full textMetalloproteases are a class of proteins very important for bacterial physiology, they are involved in many different aspects of microbial life and in the recent years they are target of many relevant studies.
Through a genomic approach, we identified three hypothetical metalloprotease in Non-typeable Haemophilus influenzae (NTHi): NT013, NT017 and NT022. These proteins belong to LytM family, which is composed by factors mainly involved in cell division and in pathogenesis.
The analysis of knockout mutant strains phenotypes confirms the role of protein NT013 and NT022 in cell splitting process; in particular we observed defective phenotypes in terms of cell morphology, formation of chains and bacterial aggregates. Moreover, we demonstrated a direct activity of protein NT013 in peptidoglycan cleavage, meanwhile NT022 seems to have a regulatory function.
Furthermore, the alteration in the cell division in the KO strains resulted in an increase in the release of Outer Membrane Vesicles (OMVs), probably due to a decrease in membrane stability.
NT017 does not seem to be involved in cell division process, but has a possible role in host colonization, since NT017 deletion reduces the capacity of NTHi to adhere to epithelial cells, to form biofilm and shows a susceptibility to human serum mediated killing.
The results obtained so far clearly highlight the importance of LytM factors in NTHi physiology and pathogenesis.Novartis Vaccine
L’evoluzione dei sistemi costieri in risposta alla dinamica fluviale ed alle oscillazioni climatiche: i casi di studio della spiaggia di Soverato e della pocket beach di Caminia di Stalettì
No full textNon heritable risk factors for Multiple Sclerosis: Epstein Barr virus and elements influencing intestinal permeability.
No full textA multicenter study on the appropriateness of hospitalization in obstetric wards:
No full textObjectives
This study has been based on the implementation of the Obstetric Appropriateness Evaluation Protocol in 7 Italian hospitals to determine inappropriate hospital admissions and days of stay.
Design
A cross-sectional study.
Methods
The outcomes examined were: appropriateness/inappropriateness of admission and "percentage of inappropriateness".
Results
A total number of 2196 clinical records were reviewed. The mean percentage of inappropriateness for a hospitalization was 22%. The percentage of inappropriateness for the first ten days of hospitalization peaked in correspondence of the 4th and 5th (42%).
The emergency admission was a protective factor of inappropriated admission, OR= 0.23 95%CI (0.16-0.35). To be hospitalized in a Teaching Hospital, in a hospital with ≥30 beds and to be admitted during the Winter/Autumn and in the workweek were risk factors of inappropriateness, respectively with OR=3.50 95%CI(2.30-5.34), OR=2.04 95%CI(1.41-2.97), OR=2.14 95%CI(1.41-2.97), OR=1.85 95%CI(1.12-3.04).
The linear regression model underlined that the "percentage of inappropriateness" significantly increased in inappropriate admission and in obstetric wards with ≥30 beds; the admission in a Teaching Hospital and the hospitalization in South Italy was inversely associated to the percentage of inappropriateness. The R2 model was 0.367.
Conclusions
The present study suggests that the percentage of inappropriate admission depends especially on the inappropriate admission and the large number of beds in obstetric wards. This suggests that the management of big hospitals, which is very complex, needs improving the processes of support and coordination of health professionals. The obstetric AEP tool seems to be an useful instrument for the decision makers to monitor and manage the obstetric wards.Nessun
The effect of LTC spending on dependent elderly people and their families' income
No full textThis work examines the economic conditions of dependent elderly people and their families, in order to investigate the existence of a relation between the condition of dependence and the risk of falling into poverty. For this purpose, we divide the research in to phase. The result of the first phase, obtained through a cluster analysis, is the definition of four typologies of the European States on the basis of LTC systems' specific aspects (public expenditure, accessibility and delivery of services and the care market composition), which in our opinion, affect the level of private resources (both in term of time and money) that dependent elderly people and their family members devote to care. On the basis of the result of the cluster analysis we selected a restrict number of countries in order to estimate the possible connection between the level of private care resources related to the health condition of the elderly and the risk of poverty, both for the dependent elderly and for their adult children. Through the use of micro data, this work offers an analysis of the impacts of the LTC system reform processes on the formal and informal services, during the last ten years. Logistic regression models are used for estimate the relationship between the risk of poverty, the private care resources, the individual and family characteristics and the benefits that the dependent elderly people receive from LTC system.
At the aggregate level, the main sources of data are represented by ESSPROS, SHA, OECD and EUROSTAT. At the micro level we use the Survey of Health, Ageing and Retirement in Europe (SHARE: wave 1, wave 2 and wave 4) to analyze both LTC-related spending and the elderly person’s and its family income. We utilize the dataset of the three waves of SHARE in order to use a diachronic approach for better understanding of the incidence of the dependent condition on the income of the elderly and their family.This research attempts to bring together two levels of analysis that have been usually considered separately in social policy studies. In diagram 1 we presents the relationships linking together the processes of reform that have interested the LTC systems at the macro level with the economic impact that they generate at the micro/individual level. Additionally, this analysis tries to consider simultaneously both the risk factors and the prevention factors related to the dependent condition, in order to assess the extent to which greater reliance on the private care resources can affect the household’s risk of poverty. The macro analysis highlights the existence of a trade-off between the two dimensions of private care resources, showing that the LTC systems are distributed on a continuum, from countries in which the families are scarcely involved in the care process, to countries in which the elderly care is almost exclusively a private matter. On the basis of these results it is possible to identify four typologies of elderly care systems. The micro analysis has allowed to better understand the consequences of the reform processes on services perception in the Swedish case, highlighting, counter-trend with macro data, how the LTC system of this countries is moving away from the Scandinavian model. This research is the first study (to the author’s knowledge) that tries to link together, in a causal relationship, two of the main social risk at EU level: the ageing population and the risk of poverty of dependent persons and their familie