Computational and Analytical Bounds for Multivariate Bernoulli Distributions

Building on a new but simple method to characterize multivariate Bernoulli variables with given means, we investigate their dependence structure. We evaluate on some computational examples whether the assumption of exchangeability is binding. This is useful in applications where exchangeability is a standard assumption, such as credit risk

Probing the partly folded states of proteins by limited proteolysis

The folding of a polypeptide chain of a relatively large globular protein into its unique three-dimensional and functionally active structure occurs via folding intermediates. These partly folded states of proteins are difficult to characterize, because they are usually short lived or exist as a distribution of possible conformers. A variety of experimental techniques and approaches have been utilized in recent years in numerous laboratories for characterizing folding intermediates that occur at equilibrium, including spectroscopic techniques, solution X-ray scattering, calorimetry and gel filtration chromatography, as well as genetic methods and theoretical calculations. In this review, we focus on the use of proteolytic enzymes as probes of the structure and dynamics of folding intermediates and we show that this simple biochemical technique can provide useful information, complementing that obtained by other commonly used techniques and approaches. The key result of the proteolysis experiments is that partly folded states (molten globules) of proteins can be sufficiently rigid to prevent extensive proteolysis and appear to maintain significant native-like structure

Professional activity, information demands, training and updating needs of occupational medicine physicians in Italy: National survey.

Objectives: Occupational medicine is a discipline continually evolving in response to technological advances, changes in workplaces and production processes, emergence of new occupational risks and diseases and modifications in regulatory framework for occupational health and safety. Therefore, the recurrent revaluation of professional activity, information demands and education and training needs of occupational physicians is essential in order to identify methodologies and tools that may contribute to improvement of their professional knowledge and competency. In this regard, we conducted the first large-scale national survey of Italian occupational medicine physicians to define their demographic and professional activity and to assess their information demands, training and updating needs. Material and Methods: A random sample of occupational physicians, listed in the national register of the Italian Ministry of Health, was selected to complete a voluntary survey. Subjects recruited in this study were asked to complete 3 different sections (personal and professional information, training and updating needs, professional activity and practice characteristics) of a questionnaire for a total of 35 questions. Results: Most of participants were specialized in occupational medicine, worked for a large number of companies and carried out health surveillance on a total number of workers that exceeds 1500. Occupational physicians would like to have a higher training offer towards practical aspects of health surveillance, risks assessment, manual handling of loads, chemical substances and upper limb biomechanical overload. Interestingly, statistically significant differences were observed subdividing the sample into different groups according to the legal requirements to perform the professional activity of occupational physicians in Italy or according to particular aspects of their professional activity. Conclusions: This study has provided interesting findings that may help to guide future discussion on alternative and additional instruments and/or methodologies that may be adopted to implement the quality and effectiveness of occupational medicine practice. Int J Occup Med Environ Health 2016;29(5):837–85

The role of lysine palmitoylation/myristoylation in the function of the TEAD transcription factors

The TEAD transcription factors are the most downstream elements of the Hippo pathway. Their transcriptional activity is modulated by different regulator proteins and by the palmitoylation/myristoylation of a specific cysteine residue. In this report, we show that a conserved lysine present in these transcription factors can also be acylated, probably following the intramolecular transfer of the acyl moiety from the cysteine. Using Scalloped (Sd), the Drosophila homolog of human TEAD, as a model, we designed a mutant protein (Glu352Gln Sd ) that is predominantly acylated on the lysine (Lys350 Sd ). This protein binds in vitro to the three Sd regulators-Yki, Vg and Tgi-with a similar affinity as the wild type Sd, but it has a significantly higher thermal stability than Sd acylated on the cysteine. This mutant was also introduced in the endogenous locus of the sd gene in Drosophila using CRISPR/Cas9. Homozygous mutants reach adulthood, do not present obvious morphological defects and the mutant protein has both the same level of expression and localization as wild type Sd. This reveals that this mutant protein is both functional and able to control cell growth in a similar fashion as wild type Sd. Therefore, enhancing the lysine acylation of Sd has no detrimental effect on the Hippo pathway. However, we did observe a slight but significant increase of wing size in flies homozygous for the mutant protein suggesting that a higher acylation of the lysine affects the activity of the Hippo pathway. Altogether, our findings indicate that TEAD/Sd can be acylated either on a cysteine or on a lysine, and suggest that these two different forms may have similar properties in cells

Early Literacy Skills and Later Reading and Writing Performance Across Countries: The Effects of Orthographic Consistency and Preschool Curriculum

Background Studies have reported a strong association between children's early literacy skills at preschool and their reading and writing skills at primary school. However, it is unclear whether this association is affected by language and curriculum practices. Objective The study investigates (i) whether early literacy skills are influenced by orthographic consistency and by preschool curriculum, and (ii) how early skills are related to later literacy skills across countries. Method Three countries, Italy (n = 73), Romania (n = 65), and Belgium (n = 109) were involved in the study, for a total of 247 children. Language and early literacy in preschool were assessed using a novel assessment tool (the ‘Talk’). Early visual-phonological and manual aspects integration were investigated using rapid automatized naming and grapho-motor tasks. The children’s reading and writing skills nine months later were assessed using standardized tests. Results Results showed higher early literacy scores for the groups of children speaking languages with more transparent orthographic systems and for the group taking part in preschool activities designed to enhance literacy acquisition. Later reading and writing skills were predicted by early competences, albeit with differences across countries. Conclusions Findings suggest that literacy acquisition trajectories are not only associated with early skills but are also influenced by language characteristics and curriculum practices. The study also presents preliminary findings relative to the ‘Talk’, an assessment tool that may have important implications for early identification and intervention of language and literacy difficulties, as well as for improving cross-country curriculum practices

Development of Surface Chemical Strategies for Synthesizing Redox-Responsive Diatomite Nanoparticles as a Green Platform for On-Demand Intracellular Release of an Antisense Peptide Nucleic Acid Anticancer Agent

Redox-responsive silica drug delivery systems are synthesized by aeco-friendly diatomite source to achieve on-demand release of peptide nucleic acid (PNA) in tumor reducing microenvironment, aiming to inhibit the immune check-point programmed cell death 1 receptor/programmed cell death receptor ligand 1 (PD-1/PD-L1) in cancer cells. The nanoparticles (NPs) are coated with polyethylene glycol chains as gatekeepers to improve their physicochemical properties and control drug release through the cleavable disulfide bonds (S-S) in a reductive environment. This study describes different chemical conditions to achieve the highest NPs' surface functionalization yield, exploring both multistep and one-pot chemical functionalization strategies. The best formulation is used for covalent PNA conjugation via the S-S bond reaching a loading degree of 306 +/- 25 mu g (PNA) mg(DNPs)(-1). These systems are used for in vitro studies to evaluate the kinetic release, biocompatibility, cellular uptake, and activity on different cancer cells expressing high levels of PD-L1. The obtained results prove the safety of the NPs up to 200 mu g mL(-1) and their advantage for controlling and enhancing the PNA intracellular release as well as antitumor activity. Moreover, the downregulation of PD-L1 observed only with MDA-MB-231 cancer cells paves the way for targeted immunotherapy.Peer reviewe

Real life turnaround time of blood cultures in the clinical microbiology laboratory: results of the first Italian survey, May 2015

Background and aims: Blood culture (BC) results are essential to guide antimicrobial chemotherapy for patients with sepsis. However, BC is a time-consuming exam, which can take several days. Reducing BCs turn around time (TAT) could impact on multiple outcome parameters and TAT monitoring is an important tool for measurement of microbiology laboratory performance. The aim of this study was to provide an overview of BC TATs among Italian microbiology laboratories. Materials and methods: Five laboratories collected and recorded, for a month period, date and time of the BC processing events. Cumulative TATs were analysed using the GraphPad software. Results: Participating laboratories reported data from 302 sepsis episodes. The median time from when the BC system produced a positive signal until Gram-stain results were reported was 7.6 hours. A rapid molecular identification and antimicrobial susceptibility testing (AST) was performed in 26.5% of BCs. Mean TAT for identification report was significantly lower when a molecular approach was adopted (12 vs. 28.7 hours, P<0.001). Similarly, results of the molecular AST were obtained more than 24 hours in advance compared with phenotypic AST (mean 13.2 vs. 47.6, P<0.001). TATs from BC positivity of laboratories opened 7 days/week were not significantly lower than those of laboratories opened 6 days/week. Conclusions: BC is a time-consuming exam, however, molecular identification and AST methods can drastically reduce time to results. The lack of difference between TATs observed for laboratories working 7 days/week and 6 days/week, coupled with a high rate of BCs turning positive during the night enable to conclude that the most urgent measure to reduce TATs is the expansion of laboratory regular duty hours