Nicola Luigi Bragazzi

Nanoproteomics enabling personalized nanomedicine.

Nucleic Acid Programmable Protein Arrays utilize a complex mammalian cell free expression system to produce proteins in situ. In alternative to fluorescent-labeled approaches a new label free method, emerging from the combined utilization of three independent and complementary nanotechnological approaches, appears capable to analyze protein function and protein-protein interaction in studies promising for personalized medicine. Quartz Micro Circuit nanogravimetry, based on frequency and dissipation factor, mass spectrometry and anodic porous alumina overcomes indeed the limits of correlated fluorescence detection plagued by the background still present after extensive washes. This could be further optimized by a homogeneous and well defined bacterial cell free expression system capable to realize the ambitious objective to quantify the regulatory protein networks in humans. Implications for personalized medicine of the above label free protein array using different test genes proteins are reported.

A proposal for including nomophobia in the new DSM-V

The Diagnostic and Statistical Manual of Mental Disorders (DSM) is considered to be the gold standard manual for assessing the psychiatric diseases and is currently in its fourth version (DSM-IV), while a fifth (DSM-V) has just been released in May 2013. The DSM-V Anxiety Work Group has put forward recommendations to modify the criteria for diagnosing specific phobias. In this manuscript, we propose to consider the inclusion of nomophobia in the DSM-V, and we make a comprehensive overview of the existing literature, discussing the clinical relevance of this pathology, its epidemiological features, the available psychometric scales, and the proposed treatment. Even though nomophobia has not been included in the DSM-V, much more attention is paid to the psychopathological effects of the new media, and the interest in this topic will increase in the near future, together with the attention and caution not to hypercodify as pathological normal behaviors.

Assessing Ebola-related web search behaviour: insights and implications from an analytical study of Google Trends-based query volumes

BackgroundThe 2014 Ebola epidemic in West Africa has attracted public interest worldwide, leading to millions of Ebola-related Internet searches being performed during the period of the epidemic. This study aimed to evaluate and interpret Google search queries for terms related to the Ebola outbreak both at the global level and in all countries where primary cases of Ebola occurred. The study also endeavoured to look at the correlation between the number of overall and weekly web searches and the number of overall and weekly new cases of Ebola.MethodsGoogle Trends (GT) was used to explore Internet activity related to Ebola. The study period was from 29 December 2013 to 14 June 2015. Pearson’s correlation was performed to correlate Ebola-related relative search volumes (RSVs) with the number of weekly and overall Ebola cases. Multivariate regression was performed using Ebola-related RSV as a dependent variable, and the overall number of Ebola cases and the Human Development Index were used as predictor variables.ResultsThe greatest RSV was registered in the three West African countries mainly affected by the Ebola epidemic. The queries varied in the different countries. Both quantitative and qualitative differences between the affected African countries and other Western countries with primary cases were noted, in relation to the different flux volumes and different time courses. In the affected African countries, web query search volumes were mostly concentrated in the capital areas. However, in Western countries, web queries were uniformly distributed over the national territory. In terms of the three countries mainly affected by the Ebola epidemic, the correlation between the number of new weekly cases of Ebola and the weekly GT index varied from weak to moderate. The correlation between the number of Ebola cases registered in all countries during the study period and the GT index was very high.ConclusionGoogle Trends showed a coarse-grained nature, strongly correlating with global epidemiological data, but was weaker at country level, as it was prone to distortions induced by unbalanced media coverage and the digital divide. Global and local health agencies could usefully exploit GT data to identify disease-related information needs and plan proper communication strategies, particularly in the case of health-threatening events.

Prototypes of Newly Conceived Inorganic and Biological Sensors for Health and Environmental Applications

This paper describes the optimal implementation of three newly conceived sensors for both health and environmental applications, utilizing a wide range of detection methods and complex nanocomposites. The first one is inorganic and based on matrices of calcium oxide, the second is based on protein arrays and a third one is based on Langmuir-Blodgett laccase multi-layers. Special attention was paid to detecting substances significant to the environment (such as carbon dioxide) and medicine (drug administration, cancer diagnosis and prognosis) by means of amperometric, quartz crystal microbalance with frequency (QCM_F) and quartz crystal microbalance with dissipation monitoring (QCM_D) technologies. The resulting three implemented nanosensors are described here along with proofs of principle and their corresponding applications.

A Google Trends-based approach for monitoring NSSI.

Non-suicidal self-injury (NSSI) is an intentional, direct, and socially unacceptable behavior resulting in the destruction of one’s own body tissues with no intention of dying or committing suicide, even though it is associated with a higher risk of attempted, planned, or just considered suicide. In this preliminary report, we introduce the concept of “NSSI 2.0”; that is to say, the study of the Internet usage by subjects with NSSI, and we introduce a Google Trends-based approach for monitoring NSSI, called NSSI infodemiology and infoveillance. Despite some limitations, Google Trends has already proven to be reliable for infectious diseases monitoring, and here we extend its application and potentiality in the field of suicidology. Ad hoc web portals and surveys could be designed in light of the reported results for helping people with NSSI.

Conductometric monitoring of protein-protein interactions.

Conductometric monitoring of protein-protein and protein-sterol interactions is here proved feasible by coupling quartz crystal microbalance with dissipation monitoring (QCM_D) to nucleic acid programmable protein arrays (NAPPA). The conductance curves measured in NAPPA microarrays printed on quartz surface allowed the identification of binding events between the immobilized proteins and the query. NAPPA allows the immobilization on the quartz surface of a wide range of proteins and can be easily adapted to generate innumerous types of biosensors. Indeed multiple proteins on the same quartz crystal have been tested and envisaged proving the possibility of analyzing the same array for several distinct interactions. Two examples of NAPPA-based conductometer applications with clinical relevance are presented herein, the interaction between the transcription factors Jun and ATF2 and the interaction between Cytochrome P540scc and cholesterol.

An overview of current and potential use of information and communication technologies for immunization promotion among adolescents

Information and communication technologies (ICT), such as the Internet or mobile telephony, have become an important part of the life of today’s adolescents and their main means of procuring information. The new generation of the Internet based on social-networking technologies, Web 2.0, is increasingly used for health purposes by both laypeople and health professionals. A broad spectrum of Web 2.0 applications provides several opportunities for healthcare workers, in that they can reach large numbers of teenagers in an individualized way and promote vaccine-related knowledge in an interactive and entertaining manner. These applications, namely social-networking and video-sharing websites, wikis and microblogs, should be monitored in order to identify current attitudes toward vaccination, to reply to vaccination critics and to establish a real-time dialog with users. Moreover, the ubiquity of mobile telephony makes it a valuable means of involving teenagers in immunization promotion, especially in developing countries.

Leveraging Big Data for Exploring Occupational Diseases-Related Interest at the Level of Scientific Community, Media Coverage and Novel Data Streams: The Example of Silicosis as a Pilot Study

Objective Silicosis is an untreatable but preventable occupational disease, caused by exposure to silica. It can progressively evolve to lung impairment, respiratory failure and death, even after exposure has ceased. However, little is known about occupational diseases-related interest at the level of scientific community, media coverage and web behavior. This article aims at filling in this gap of knowledge, taking the silicosis as a case study. Methods We investigated silicosis-related web-activities using Google Trends (GT) for capturing the Internet behavior worldwide in the years 2004–2015. GT-generated data were, then, compared with the silicosis-related scientific production (i.e., PubMed and Google Scholar), the media coverage (i.e., Google news), the Wikipedia traffic (i.e, Wikitrends) and the usage of new media (i.e., YouTube and Twitter). Results A peak in silicosis-related web searches was noticed in 2010–2011: interestingly, both scientific articles production and media coverage markedly increased after these years in a statistically significant way. The public interest and the level of the public engagement were witnessed by an increase in likes, comments, hashtags, and re-tweets. However, it was found that only a small fraction of the posted/uploaded material contained accurate scientific information. Conclusions GT could be useful to assess the reaction of the public and the level of public engagement both to novel risk-factors associated to occupational diseases, and possibly related changes in disease natural history, and to the effectiveness of preventive workplace practices and legislative measures adopted to improve occupational health. Further, occupational clinicians should become aware of the topics most frequently searched by patients and proactively address these concerns during the medical examination. Institutional bodies and organisms should be more present and active in digital tools and media to disseminate and communicate scientifically accurate information. This manuscript should be intended as preliminary, exploratory communication, paving the way for further studies.

Direct and indirect comparison meta-analysis of levetiracetam versus phenytoin or valproate for convulsive status epilepticus.

AIM The aim of this study was to conduct a meta-analysis of published studies to directly compare intravenous (IV) levetiracetam (LEV) with IV phenytoin (PHT) or IV valproate (VPA) as second-line treatment of status epilepticus (SE), to indirectly compare intravenous IV LEV with IV VPA using common reference-based indirect comparison meta-analysis, and to verify whether results of indirect comparisons are consistent with results of head-to-head randomized controlled trials (RCTs) directly comparing IV LEV with IV VPA. METHODS Random-effects Mantel-Haenszel meta-analyses to obtain odds ratios (ORs) for efficacy and safety of LEV versus VPA and LEV or VPA versus PHT were used. Adjusted indirect comparisons between LEV and VPA were used. RESULTS Two RCTs comparing LEV with PHT (144 episodes of SE) and 3 RCTs comparing VPA with PHT (227 episodes of SE) were included. Direct comparisons showed no difference in clinical seizure cessation, neither between VPA and PHT (OR: 1.07; 95% CI: 0.57 to 2.03) nor between LEV and PHT (OR: 1.18; 95% CI: 0.50 to 2.79). Indirect comparisons showed no difference between LEV and VPA for clinical seizure cessation (OR: 1.16; 95% CI: 0.45 to 2.97). Results of indirect comparisons are consistent with results of a recent RCT directly comparing LEV with VPA. CONCLUSION The absence of a statistically significant difference in direct and indirect comparisons is due to the lack of sufficient statistical power to detect a difference. Conducting a RCT that has not enough people to detect a clinically important difference or to estimate an effect with sufficient precision can be regarded a waste of time and resources and may raise several ethical concerns, especially in RCT on SE.

SMILE silencing and PMA activation gene networks in hela cells: Comparison with kidney transplantation gene networks†

Recent findings indicated that the SMILE gene may be involved in kidney graft operational tolerance in human. This gene was found to be up‐regulated in blood from patients with a well functioning kidney transplant in the absence of immunosuppression compared to other transplanted recipients with clinically different status. A microarray study of SMILE knock‐down and phorbol 12‐myristate 13‐acetate (PMA) activation in HeLa cells was herein compared to our earlier analysis based on microarray data of kidney allograft tolerance and rejection in humans and in a rat model of allograft transplantation to determine possible new genes and gene networks involved in kidney transplantation. The nearest neighbors at the intersection of the SMILE knock‐down network with the human tolerance/rejection networks are shown to be NPHS1 and ARRB2, the former (Nephrin) being involved in kidney podocyte function, and the decrease of the latter (Arrestin β2) being recently shown to be involved in monocyte activation during acute kidney allograft rejection in rat. Moreover, another one of the neighbors at the intersection of SMILE network and tolerance/rejection networks is XBP‐1, that we report previously to be increased, at a transcript level, after ER stress in SMILE silenced cells. Finally, in this study, we also show that topological properties (both local and global) of joint SMILE knock‐down network—tolerance/rejection networks and joint PMA activation network—tolerance/rejection networks in rat and human are essentially different, likely due to the inherent nature of the gene SMILE and the mitogen PMA, that do not act the same way on genes and do not interfere the same way on networks. We also show that interestingly SMILE networks contain more feed‐forward loop (FFL) motifs and thus SMILE calls for a more fine‐tuned genetic regulation. J. Cell. Biochem. 113: 1820–1832, 2012.