(a cura di) Manuale di tecniche diagnostiche ed esami di laboratorio / Wilson Denise

Il Manuale di Tecniche Diagnostiche ed Esami di Laboratorio di McGraw-Hill illustra in maniera specifica tutto ciò che è necessario conoscere sulla corretta indicazione all'utilizzo e all'interpretazione degli esami diagnostici. Affronta inoltre il tema della preparazione del paziente nelle fasi di esecuzione e che precedono e seguono l'esame, allo scopo di fornirgli un'assistenza scrupolosa e attenta alle diverse normative relative alla sicurezza. Il Manuale, di agile formato e facile consultazione, rappresenta l'unico testo interamente pensato e costruito a partire dalle linee guida della pratica professionale basate sulle evidenze scientifiche, un valido motivo in più per utilizzarlo con successo nella pratica clinica quotidiana

Fatigue behavior of stiffener to cross beam joints in orthotropic steel decks

In the paper the possibility to evaluate the fatigue strength of stiffener to cross beam joints in orthotropic steel decks is discussed. The proposed methodology, based on Paris-Erdogan law, allows to derive a sound estimate of the stress intensity factor K combining the indirect approach, based on the Rice J-integral, with the direct one, based on the extrapolation of experimental or numerical data. The practical implementation of the proposed methodology allowed to predict correctly the actual fatigue life of a previously tested real scale specimen, so validating its potentialities

Commento all’articolo di Mario Perini ‘Sulla violenza in sanità. Tra la violenza contro i curanti e la violenza delle cure’

L’articolo di Mario Perini è interessante e ricco di tracce per ulteriori approfondimenti. In questo contributo proverò ad evidenziare per punti, alcune linee rilevanti per la sanità rimandando ad altri scritti l’analisi del recente omicidio della psichiatra Barbara Capovani. [...

Editorial: Computational Methods for Analysis of DNA Methylation Data

DNA methylation is among the most studied epigenetic modifications in eukaryotes. The interest in DNA methylation stems from its role in development, as well as its well- established association with phenotypic changes. Particularly, there is strong evidence that methylation pattern alterations in mammals are linked to developmental disorders and cancer (Kulis and Esteller, 2010). Owing to its potential as a prognostic marker for preventive medicine, in recent years, the analysis of DNA methylation data has garnered interest in many different contexts of computational biology (Bock, 2012). As it typically happens with omic data, processing, analyzing and interpreting large-scale DNA methylation datasets requires computational methods and software tools that address multiple challenges. In the present Research Topic, we collected papers that tackle different aspects of computational approaches for the analysis of DNA methylation data. These manuscripts address novel computational solutions for copy number variation detection, cell-type deconvolution and methylation pattern imputation, while others discuss interpretations of well-established computational techniques. Over the last 10 years, DNA methylation profiles have been successfully exploited to develop biomarkers of age, also referred to as epigenetic clocks (Bell et al., 2019). Epigenetic clocks accurately estimate both chronological and biological age from methylation levels. DNA methylation age and, most importantly, its deviation from chronological age have been shown to be associated with a variety of health issues. More recently, a second generation of epigenetic clocks has emerged. The new generation of clocks incorporates not only methylation profiles but also environmental variants, such as smoking and alcohol consumption, and they outperform the first generation in mortality prediction and prognosis of certain diseases. In our collection, the review by Chen et al. compares the first and second generation of epigenetic clocks that predict cancer risk and discusses pathways known to exhibit altered methylation in aging tissues and cancer. Differentially methylated regions (DMRs), that is genomic regions that show significant differences in methylation levels across distinct biological and/or medical conditions (e.g., normal vs. disease), have been reported to be implicated in a variety of disorders (Rakyan et al., 2011). As a result, identifying DMRs is one of the most critical and fundamental challenges in deciphering disease mechanisms at the molecular level. Although DNA methylation patterns remain stable during normal somatic cell growth, alterations in genomic methylation may be caused by genetic alterations, or vice versa. However, standard DMR analysis often ignores whether methylation alterations should be viewed as a cause or an effect. Rhamani et al. discuss the effect of model directionality, i.e. whether the condition of interest (phenotype) may be affected by methylation or whether it may affect methylation, in differential methylation analyses at the cell-type level. They show that correctly accounting for model directionality has a significant impact on the ability to identify cell type specific differential methylation. Different cell types exhibit DMRs at many genomic regions and such rich information can be exploited to infer underlying cell type proportions using deconvolution techniques. DNA methylation-based cell mixture deconvolution approaches can be classified into two main categories: reference-based and reference-free. While the latter are more broadly applicable, as they do not rely on the availability of methylation profiles from each of the purified cell types that compose a tissue of interest, they are also less precise. Reference-based approaches use DMRs specific to cell types (reference library) to determine the underlying cellular composition within a DNA methylation sample. The quality of the reference library has a big impact on the accuracy of reference-based approaches. Bell-Glenn et al. present RESET, a framework for reference library selection for deconvolution algorithms exploiting a modified version of the Dispersion Separability Criteria score, for the inference of the best DMRs composing the library, contributing to de facto standards (Koestler et al., 2016). In short, RESET does not require researchers to identify a priori the size of the reference library (number of DMRs), nor to rely on costly associated purified cells’ mDNA profiles. Within a cellular population, the methylation patterns of different cell types and at specific genomic locations are indicative of cellular heterogeneity. Alterations of such heterogeneity are predictive of development as well as prognostic markers of diseases. Computational methods that exploit heterogeneity in methylation patterns are typically constrained by partially observed patterns due to the nature of shotgun sequencing, which frequently generates limited coverage for downstream analysis. One possible solution to overcome such limitations is offered by Chang et al. presenting BSImp, a probabilistic based imputation method that uses local information to impute partially observed methylation patterns. They show that using this approach they are able to recover heterogeneity estimates at 15% more regions with moderate sequencing depths. This should therefore improve our ability to study how methylation heterogeneity is associated with disease. Finally, recent studies have shown how the associations between Copy Number Variations (CNVs) and methylation alterations offer a richer and hence more informative picture of the samples under study, in particular for tumor data characterized by large scale genomic rearrangements (Sun et al., 2018). Consequently, recent technological and methodological developments have enabled the possibility to measure CNVs from DNA methylation data. The main advantage of DNA methylation based CNV approaches is that they offer the possibility to integrate both genomic (copy number) and epigenomic (methylation) information. Mariani et al. propose MethylMasteR, an R software package that integrates DNA methylation-based CNV calling routines, facilitating standardization, comparison and customization of CNV analyses. This package, built into the Docker architecture to seamlessly mange dependencies, includes four of the most commonly used routines for this integrated analysis, ChAMP (Morris et al., 2014), SeSAMe (Zhou et al., 2018), Epicopy (Cho et al., 2019), plus a custom version of cnAnalysis450k (Knoll et al., 2017), overall enabling analysis of comparative results. All the topics in this issue, although limited to specific aspects of DNA methylation analysis, highlight the importance of research in this field, the associated computational challenges and illustrate the significant impact that this type of data will likely have on preventive medicine

Higher harmonic inverse free-electron laser interaction

We expand the theory of the inverse free electron laser (IFEL) interaction to include the possibility of energy exchange that takes place when relativistic particles traversing an undulator interact with an electromagnetic wave of a frequency that is a harmonic of the fundamental wiggler resonant frequency. We derive the coupling coefficients as a function of the IFEL parameters for all harmonics, both odd and even. The theory is supported by simulation results obtained with a three-dimensional Lorentz equation solver code. Comparisons are made between the results of theory and simulations, and the recent UCLA IFEL experimental results where higher harmonic IFEL interaction was observed

Psychiatric Emergency in Children and Adolescents: A Retrospective Study in Parma Local Health Unit

The mental health care system in Italy is based on Law 180/70 which leaves great regional autonomy about the management of adolescent patients suffering from psychiatric diseases. The aim of this study is the evaluation of demographic, social, and clinical features of minors admitted to psychiatric wards, as starting point to improve individualized services for them. Data about all under 18s consecutively admitted to Parma’s psychiatric wards from 2013 to 2015 were retrospectively collected from medical records. Diagnoses were classified according to ICD-10 criteria, and statistical analysis was performed using SPSS statistical software (IBM SPSS Statistics 22.0) for Windows. Clinical samples include 51 cases, 30 males (mean age: 15.5 years, ranging from 12 to 17 years) and 21 females (mean age: 15.9, ranging from 14 to 17 years). The most frequent diagnosis is conduct disorder (39.2%), with higher prevalence among males. Following this, 23.5% of the patients present comorbidity issues and 9.8% suffer from personality disorders, which is more frequent among females. High percentages of foreigners (31.4%), adopted minors (15.7%), and drug users (40%) are reported. Furthermore, data reveal that unprotective family environment, registered in 80.4% of cases, plays an important role as risk factor for the development of mental disease, readmissions in psychiatric wards, and discharge to residential facilities. Readmissions, as well as compulsory treatments (11 cases), are mainly required in case of conduct disorders and comorbidity diagnosis. Lastly, in contrast with the situation before hospital admission, most patients (63.3%) are discharged and sent to community residential facilities. Findings can be useful to improve the management of psychiatric emergencies in minors, focusing on their specific needs, such as conduct disorders and substance abuse, and to face emerging challenges, for example, mental health disease associated with the growing phenomenon of immigration

von Willebrand factor-binding protein (vWbp)-activated factor XIII and transglutaminase 2 (TG2) promote cross-linking between FnBPA from Staphylococcus aureus and fibrinogen

The secreted von Willebrand factor-binding protein (vWbp) from Staphylococcus aureus interacts with the coagulation factors prothrombin and fibrinogen (Fbg), leading to the non-proteolytic transglutaminase activation of Factor XIII (FXIII). In this study we found that vWbp-activated FXIII catalyses the incorporation of amino-donor dansylcadaverine into region A of fibronectin-binding protein A (FnBPA). Incubation of Fbg with recombinant region A of S. aureus Fbg-binding proteins FnBPA, FnBPB, ClfA or ClfB in presence of vWbp-activated FXIII resulted in the formation of high molecular heteropolymers with FnBPA only, suggesting a specificity of the cross-linking reaction between fibrin(ogen) and the staphylococcal surface. As previously observed, cross-linking sites were mapped to the α-chain and the N1 subdomain of fibrin(ogen) and region A of FnBPA, respectively. Comparable results were obtained when tissue tranglutaminase-2 (TG2) was tested for cross-linking of FnBPA and Fbg. Of note, FnBPA-mediated covalent cross-linking promoted by vWbp-activated FXIII was also observed when bacteria were allowed to attach to fibrin(ogen). Together these findings suggest a novel pathogenetic mechanism by which the transglutaminase action of FXIII and/or TG2 contributes to entrapment and persistence of S. aureus in blood and host tissues

Is depressed mood clinically relevant at the onset of schizophrenia? A longitudinal study.

Aim: Depressed mood (DM) in schizophrenia is often associated with suicide risk and poor outcomes. However, it is generally overlooked in clinical practice, especially in First Episode Schizophrenia (FES). The aims of this investigation were: (1) to calculate baseline prevalence of FES patients with relevant DM, (2) to longitudinally monitor DM severity levels over a 12-month follow-up, and (3) to investigate their associations with clinical data and the specific treatment components of an “Early Intervention in Psychosis” (EIP) program. Material and Methods: The Positive and Negative Syndrome Scale (PANSS) was completed by all FES participant. Individuals with a baseline PANSS “Depression” item subscore of ≥ 5 were classified as having relevant depressed mood (FES/DM+). Chi-square and Mann-Whitney tests were used for inter-group comparisons. A linear regression analysis was also performed. Results: Fifty-three (33.3%) participants were in the FES/DM+ subgroup. Relevant DM at baseline was associated with female gender and a higher PANSS “Positive Symptoms” score. Across the follow-up, FES individuals improved their DM severity levels. This was significantly related to a longitudinal decrease in PANSS “Positive Symptoms” levels. Conclusions: DM is relatively frequent in FES, already at the recruitment in EIP services. However, its severity decreases overtime within specialized EIP programs

The iron-regulated surface determinant B (IsdB) protein from Staphylococcus aureus acts as a receptor for the host protein vitronectin.

Staphylococcus aureus is an important bacterial pathogen that can cause a wide spectrum of diseases in humans and other animals. S. aureus expresses a variety of virulence factors that promote infection with this pathogen. These include cell-surface proteins that mediate adherence of the bacterial cells to host extracellular matrix components, such as fibronectin and fibrinogen. Here, using immunoblotting, ELISA, and surface plasmon resonance analysis, we report that the iron-regulated surface determinant B (IsdB) protein, besides being involved in heme transport, plays a novel role as a receptor for the plasma and extracellular matrix protein vitronectin (Vn). Vn-binding activity was expressed by staphylococcal strains grown under iron starvation conditions when Isd proteins are expressed. Recombinant IsdB bound Vn dose dependently and specifically. Both near-iron transporter motifs NEAT1 and NEAT2 of IsdB individually bound Vn in a saturable manner, with KD values in the range of 16-18 nm Binding of Vn to IsdB was specifically blocked by heparin and reduced at high ionic strength. Furthermore, IsdB-expressing bacterial cells bound significantly higher amounts of Vn from human plasma than did an isdB mutant. Adherence to and invasion of epithelial and endothelial cells by IsdB-expressing S. aureus cells was promoted by Vn, and an αvβ3 integrin-blocking mAb or cilengitide inhibited adherence and invasion by staphylococci, suggesting that Vn acts as a bridge between IsdB and host αvβ3 integrin