Oli essenziali ad attivita' antimalarica

Oli essenziali ad attivita' antimalaric

Towards the insulator-to-metal transition at the surface of ion-gated nanocrystalline diamond films

Hole doping can control the conductivity of diamond either through boron substitution, or carrier accumulation in a field-effect transistor. In this work, we combine the two methods to investigate the insulator-to-metal transition at the surface of nanocrystalline diamond films. The finite boron doping strongly increases the maximum hole density which can be induced electrostatically with respect to intrinsic diamond. The ionic gate pushes the conductivity of the film surface away from the variable-range hopping regime and into the quantum critical regime. However, the combination of the strong intrinsic surface disorder due to a non-negligible surface roughness, and the introduction of extra scattering centers by the ionic gate, prevents the surface accumulation layer to reach the metallic regime.Comment: 5 pages, 4 figure

Towards the insulator-to-metal transition at the surface of ion-gated nanocrystalline diamond films

Hole doping can control the conductivity of diamond either through boron substitution, or carrier accumulation in a field-effect transistor. In this work, we combine the two methods to investigate the insulator-to-metal transition at the surface of nanocrystalline diamond films. The finite boron doping strongly increases the maximum hole density which can be induced electrostatically with respect to intrinsic diamond. The ionic gate pushes the conductivity of the film surface away from the variable-range hopping regime and into the quantum critical regime. However, the combination of the strong intrinsic surface disorder due to a non-negligible surface roughness, and the introduction of extra scattering centers by the ionic gate, prevents the surface accumulation layer to reach the metallic regime.Comment: 5 pages, 4 figure

An extra dimension in protein tagging by quantifying universal proteotypic peptides using targeted proteomics

The use of protein tagging to facilitate detailed characterization of target proteins has not only revolutionized cell biology, but also enabled biochemical analysis through efficient recovery of the protein complexes wherein the tagged proteins reside. The endogenous use of these tags for detailed protein characterization is widespread in lower organisms that allow for efficient homologous recombination. With the recent advances in genome engineering, tagging of endogenous proteins is now within reach for most experimental systems, including mammalian cell lines cultures. In this work, we describe the selection of peptides with ideal mass spectrometry characteristics for use in quantification of tagged proteins using targeted proteomics. We mined the proteome of the hyperthermophile Pyrococcus furiosus to obtain two peptides that are unique in the proteomes of all known model organisms (proteotypic) and allow sensitive quantification of target proteins in a complex background. By combining these 'Proteotypic peptides for Quantification by SRM' (PQS peptides) with epitope tags, we demonstrate their use in co-immunoprecipitation experiments upon transfection of protein pairs, or after introduction of these tags in the endogenous proteins through genome engineering. Endogenous protein tagging for absolute quantification provides a powerful extra dimension to protein analysis, allowing the detailed characterization of endogenous proteins

Bone damage after chemotherapy for lymphoma: a real-world experience

Abstract Background: Despite recent improvements in survival due to advances in treatment, the quality of life of patients with lymphoma may be compromised by the long-term complications of chemotherapy and steroid therapy. Among these, a potentially relevant problem is bone loss and the development of fragility fractures. Aim: To provide further evidence of clinical or subclinical skeletal complications in correlation with biological variables and markers of bone disease in patients with complete response to therapy. Method: A cross-sectional observational study was conducted on subjects diagnosed with lymphoma with subsequent antineoplastic treatment, disease status after therapy defined as complete response disease for at least a year now. We performed: blood chemistry tests, imaging techniques and screening tools for the assessment of functional status and quality of life (SARC-F and mini-Osteoporosis Quality of Life). Results: Approximately 50% of patients had osteoporosis, with a prevalence of vertebral fractures of 65.5%. In most patients, we found hypovitaminosis D and high levels of parathyroid hormone (PTH). Furthermore, a statistically significant association was observed between high PTH levels and previous lymphoma treatment. Finally, the MiniOsteoporosis Quality of life (mini-OQLQ) questionnaire demonstrated a loss of quality of life as a consequence of the change in bone status. Conclusions: Patient treatment design for personalized chemotherapy would be desirable to reduce late effects on bone. Also, early prevention programs need to be applied before starting treatment. The most benefited subpopulations could be not only elderly but also young patients

Identification of quantitative proteomic differences between Mycobacterium tuberculosis lineages with altered virulence

Evidence currently suggests that as a species Mycobacterium tuberculosis exhibits very little genomic sequence diversity. Despite limited genetic variability, members of the M. tuberculosis complex (MTBC) have been shown to exhibit vast discrepancies in phenotypic presentation in terms of virulence, elicited immune response and transmissibility. Here, we used qualitative and quantitative mass spectrometry tools to investigate the proteomes of seven clinically-relevant mycobacterial strains four M. tuberculosis strains, M. bovis, M. bovis BCG, and M. avium that show varying degrees of pathogenicity and virulence, in an effort to rationalize the observed phenotypic differences. Following protein preparation, liquid chromatography mass spectrometry (LC MS/MS) and data capture were carried out using an LTQ Orbitrap Velos. Data analysis was carried out using a novel bioinformatics strategy, which yielded high protein coverage and was based on high confidence peptides. Through this approach, we directly identified a total of 3788 unique M. tuberculosis proteins out of a theoretical proteome of 4023 proteins and identified an average of 3290 unique proteins for each of the MTBC organisms (representing 82% of the theoretical proteomes), as well as 4250 unique M. avium proteins (80% of the theoretical proteome). Data analysis showed that all major classes of proteins are represented in every strain, but that there are significant quantitative differences between strains. Targeted selected reaction monitoring (SRM) assays were used to quantify the observed differential expression of a subset of 23 proteins identified by comparison to gene expression data as being of particular relevance to virulence. This analysis revealed differences in relative protein abundance between strains for proteins which may promote bacterial fitness in the more virulent W. Beijing strain. These differences may contribute to this strain's capacity for surviving within the host and resisting treatment, which has contributed to its rapid spread. Through this approach, we have begun to describe the proteomic portrait of a successful mycobacterial pathogen. Data are available via ProteomeXchange with identifier PXDO04165

Patient-Reported Outcomes After Swallowing (SWOARs)-Sparing IMRT in Head and Neck Cancers: Primary Results from a Prospective Study Endorsed by the Head and Neck Study Group (HNSG) of the Italian Association of Radiotherapy and Clinical Oncology (AIRO)

Objectives To prospectively investigate changes in M.D. Anderson Dysphagia Inventory (MDADI) scores in patients affected by naso- and oropharynx cancer after definitive radiochemotherapy (ChemoRT) using swallowing organs at risk (SWOARs)-sparing IMRT. Methods MDADI questionnaires were collected at baseline and at 6 and 12 months after treatment. MDADI scores were categorized as follows: >= 80 "optimal," 80-60 "adequate," < 60 "poor" deglutition-related quality of life (QoL) group, and dichotomized as "optimal" vs "adequate/poor" for the analysis. A mean MDADI composite (MDADI-C) change of 10 points was considered as minimal clinically important difference (MCID). Results Sixty-three patients were enrolled of which 47 were considered for the analysis. At baseline, 26 (55%) were "optimal" and 21 (45%) were "adequate/poor." The mean baseline MDADI-C score was 93.6 dropping to 81 at 6 months (p = 0.013) and slightly rising to 85.5 at 12 months (p = 0.321) for the "optimal" group. Indeed, the mean baseline MDADI-C score was 64.3 rising to 77.5 at 6 months (p = 0.006) and stabilizing at 76 at 12 months (p = 0.999) for the "adequate/poor" group. A statistically significant but not clinically relevant worsening of the MDADI-C score was reported for the "optimal" group, whereas both a statistically significant and clinically meaningful improvement of the MDADI-C score were reported for the "adequate/poor" group from before to post-treatment. Conclusion Our results suggest a doubly clinical benefit of dose optimization to SWOARs to minimize the RT sequalae in patients with a baseline "optimal" deglutition-related QoL and to recover from cancer dysphagia in those with a baseline "adequate/poor" deglutition-related QoL

Delocalizzazione della sperimentazione clinica: questioni etiche

Fino agli anni'80 la maggior parte delle sperimentazioni cliniche veniva svolta esclusivamente nei Paesi sviluppati. Successivamente si è assistito ad una progressiva delocalizzazione delle sperimentazioni cliniche verso i Paesi in via di sviluppo dove si hanno costi più favorevoli, regolamenti meno rigorosi e maggiore disponibilità di pazienti. Tale processo ha generato non poche criticità etiche, tra le quali: spesso la partecipazione agli studi clinici rapresenta l'unica opportunità di cura, raramente gli studi clinici sponsorizzati da Paesi sviluppati rispondono alle esigenze sanitarie dei Paesi in via di sviluppo in cui vengono condotti, frequentemente si riscontra un utilizzo improprio del placebo nel braccio di controllo degli studi randomizzati e raramente viene garantito l'accesso alle cure una volta terminato lo studio clinico. Tali questioni etiche generano la necessità di un aggiornamento che semplifichi le linee guida esistenti, tenendo conto delle specificità dei diversi contesti in cui viene svolta la sperimentazione clinica. Until 1980s, most clinical trials were exclusively conducted in developed countries. Then there has been a progressive delocalization of clinical trials to developing countries, where more favorable costs, less rigorous regulations and greater availability of patients are present. This ongoing process has generated many ethical issues, among which: participation in clinical trials often represents the only treatment opportunity for patients, rarely clinical trials sponsored by developed countries respond to the health needs of the developing countries in which they are conducted, frequent improper use of placebo control arms in randomized trials, and access to treatment is rarely guaranteed at the end of clinical trials. These ethical issues generate the need for updated and simplified guidelines that take into account the unique features of the different countries where the clinical trial is carried out

Structure-based mutant stability predictions on proteins of unknown structure.

The ability to rapidly and accurately predict the effects of mutations on the physicochemical properties of proteins holds tremendous importance in the rational design of modified proteins for various types of industrial, environmental or pharmaceutical applications, as well as in elucidating the genetic background of complex diseases. In many cases, the absence of an experimentally resolved structure represents a major obstacle, since most currently available predictive software crucially depend on it. We investigate here the relevance of combining coarse-grained structure-based stability predictions with a simple comparative modeling procedure. Strikingly, our results show that the use of average to high quality structural models leads to virtually no loss in predictive power compared to the use of experimental structures. Even in the case of low quality models, the decrease in performance is quite limited and this combined approach remains markedly superior to other methods based exclusively on the analysis of sequence features.Journal ArticleSCOPUS: ar.jinfo:eu-repo/semantics/publishe