The European cross-border health data exchange roadmap: case study in the Italian setting

Health data exchange is a major challenge due to the sensitive information and the privacy issues entailed. Considering the European context, in which health data must be exchanged between different European Union (EU) Member States, each having a different national regulatory framework as well as different national healthcare structures, the challenge appears even greater. Europe has tried to address this challenge via the epSOS (“Smart Open Services for European Patients”) project in 2008, a European large-scale pilot on cross-border sharing of specific health data and services. The adoption of the framework is an ongoing activity, with most Member States planning its implementation by 2020. Yet, this framework is quite generic and leaves a wide space to each EU Member State regarding the definition of roles, processes, workflows and especially the specific integration with the National Infrastructures for eHealth. The aim of this paper is to present the current landscape of the evolving eHealth infrastructure for cross-border health data exchange in Europe, as a result of past and ongoing initiatives, and illustrate challenges, open issues and limitations through a specific case study describing how Italy is approaching its adoption and accommodates the identified barriers. To this end, the paper discusses ethical, regulatory and organizational issues, also focusing on technical aspects, such as interoperability and cybersecurity. Regarding cybersecurity aspects per se, we present the approach of the KONFIDO EU-funded project, which aims to reinforce trust and security in European cross-border health data exchange by leveraging novel approaches and cutting-edge technologies, such as homomorphic encryption, photonic Physical Unclonable Functions (p-PUF), a Security Information and Event Management (SIEM) system, and blockchain-based auditing. In particular, we explain how KONFIDO will test its outcomes through a dedicated pilot based on a realistic scenario, in which Italy is involved in health data exchange with other European countries

Plasma Brain-Derived Neurotrophic Factor Levels Predict the Clinical Outcome of Depression Treatment in a Naturalistic Study

Remission is the primary goal of treatment for major depressive disorder (MDD). However, some patients do not respond to treatment. The main purpose of this study was to determine whether brain-derived neurotrophic factor (BDNF) levels are correlated with treatment outcomes. In a naturalistic study, we assessed whether plasma BDNF levels were correlated with clinical outcomes by measuring plasma BDNF in patients with depressive syndrome (MADRS score ≥18), and subsequently comparing levels between the subgroup of patients who underwent remission (MADRS score ≤8) and the subgroup who were refractory to treatment (non-responders). Patients with depressive syndrome who underwent remission had significantly higher plasma BDNF levels (p<0.001), regardless of age or sex. We also found a significant negative correlation between MADRS scores and plasma BDNF levels within this group (ρ = –0.287, p = 0.003). In contrast, non-responders had significantly lower plasma BDNF levels (p = 0.029). Interestingly, plasma BDNF levels in the non-responder group were significantly higher than those in the remission group in the initial stage of depressive syndrome (p = 0.002). Our results show that plasma BDNF levels are associated with clinical outcomes during the treatment of depression. We suggest that plasma BDNF could potentially serve as a prognostic biomarker for depression, predicting clinical outcome

Effects of Transmitters and Amyloid-Beta Peptide on Calcium Signals in Rat Cortical Astrocytes: Fura-2AM Measurements and Stochastic Model Simulations

BACKGROUND: To better understand the complex molecular level interactions seen in the pathogenesis of Alzheimer's disease, the results of the wet-lab and clinical studies can be complemented by mathematical models. Astrocytes are known to become reactive in Alzheimer's disease and their ionic equilibrium can be disturbed by interaction of the released and accumulated transmitters, such as serotonin, and peptides, including amyloid- peptides (A). We have here studied the effects of small amounts of A25-35 fragments on the transmitter-induced calcium signals in astrocytes by Fura-2AM fluorescence measurements and running simulations of the detected calcium signals. METHODOLOGY/PRINCIPAL FINDINGS: Intracellular calcium signals were measured in cultured rat cortical astrocytes following additions of serotonin and glutamate, or either of these transmitters together with A25-35. A25-35 increased the number of astrocytes responding to glutamate and exceedingly increased the magnitude of the serotonin-induced calcium signals. In addition to A25-35-induced effects, the contribution of intracellular calcium stores to calcium signaling was tested. When using higher stimulus frequency, the subsequent calcium peaks after the initial peak were of lower amplitude. This may indicate inadequate filling of the intracellular calcium stores between the stimuli. In order to reproduce the experimental findings, a stochastic computational model was introduced. The model takes into account the major mechanisms known to be involved in calcium signaling in astrocytes. Model simulations confirm the principal experimental findings and show the variability typical for experimental measurements. CONCLUSIONS/SIGNIFICANCE: Nanomolar A25-35 alone does not cause persistent change in the basal level of calcium in astrocytes. However, even small amounts of A25-35, together with transmitters, can have substantial synergistic effects on intracellular calcium signals. Computational modeling further helps in understanding the mechanisms associated with intracellular calcium oscillations. Modeling the mechanisms is important, as astrocytes have an essential role in regulating the neuronal microenvironment of the central nervous system

Manipulating the Hype: contemporary art's response to media cliches

Manipulating the Hype addresses art’s reaction to the barrage of signs produced by the media. The paper researches contemporary art’s response to clichéd media stereotypes and elucidates artists’ multifaceted perspective on overtly obvious yet widely embraced paradigms marketed by the media. Contemporary art’s strategic reconfiguration of media stereotypes is a valuable introspection upon the superficiality and impracticability of advertising and entertainment industry constructs. By reconsidering the mediated image, art has the ability to inspire reevaluation of cultural values. The thesis additionally attempts to ascertain the reinterpretation of media stereotypes as a common thread linking principal art movements and historically significant artworks from around the world since 1960. How does contemporary art respond to the extensive cultural influence of the media? Is a reaction to mass media a thematic commonality linking contemporary artists in the age of globalization? Manipulating the Hype is a dual outcome investigation comprised of written thesis and studio practice. The written thesis combines experience from a lengthy professional practice with historical and theoretical research. The visual thesis consists of twelve photographic works taken at on the Big Island of Hawaii. The images juxtapose artificial icons of power from popular culture with the natural force of the active lava flow. The process of research discloses how the advertising and entertainment industries capitalize upon innate human desires through the manipulative proliferation of archetypal imagery. Furthermore, the thesis establishes the widespread retort to media clichés as a palpable commonality in studio practices worldwide. The findings in the research make evident that although contemporary art does not have sufficient influence to reform the media, it can heighten public awareness of media tactics

Regulation of GSK-3 Activity as A Shared Mechanism in Psychiatric Disorders

Serin/Treonin kinaz ailesinin üyelerinden bir kinaz olarak ilk kez glikojen sentaz’ı inhibe ettiği keşfedilen glikojen sentaz kinaz-3 (GSK-3), günümüzde bilinen 50’den fazla substratı ile birçok hücre içi düzenleyici mekanizmada görev alan geniş etki spektrumlu bir enzim olarak kabul edilmektedir. GSK-3’ün memelilerde GSK-3α ve GSK-3β olmak üzere yapısal olarak yüksek homoloji gösteren iki izoformu bulunmaktadır. Her iki izoform birçok dokuda yaygın dağılım göstermekle beraber, en yüksek oranda beyinde bulunmakta ve genellikle benzer fonksiyonlar göstermektedirler. Diğer protein kinazların aksine GSK-3 uyarılmamış hücrede yapısal olarak aktif yani defosforile halde bulur. Protein kinaz A (PKA), protein kinaz B (PKB;AKT) ve protein kinaz C (PKC) gibi diğer protein kinazlarla fosforilasyona uğrayarak olarak inaktive edilir. Günümüzde artmış GSK-3 aktivitesinin major depresyon, bipolar bozukluk, hiperaktivite bozuklukları gibi hastalıklar ve şizofreni oluşumunda rol oynayabileceğine ilişkin önemli bulgular mevcuttur. Bu nedenle söz konusu psikiyatrik hastalıklarda arttığı gösterilen GSK-3 aktivitesinin azaltılmasının tedavide umut verici bir yaklaşım olabileceği kabul edilebilir. Bu gözden geçirme çalışmasında yukarıda sözü edilen psikiyatrik hastalıkların oluşmasında görev alan GSK-3 aracılı mekanizmalara kısaca değinilerek GSK-3’ün aktivitesinin düzenlenmesinde rol oynadığı gösterilen klinikte kullanılan ilaçlara yer verilmiştir. Anahtar sözcükler: GSK-3, depresyon, bipolar bozukluk, şizofren

Innovative analysis of diazepam and metabolites in rat brain and plasma using an original MEPS \u2013 HPLC method

Diazepam (7-chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one) is one of the most widely used anxiolytic-hypnotic drugs. It is a long-acting benzodiazepine with anxiolytic, sedative, hypnotic, anticonvulsant, muscle relaxant and amnestic properties. Diazepam is also frequently used for the relief of anxiety during the first period of treatment with selective serotonin reuptake inhibitors (SSRIs) and generally as a coadjuvant during antidepressive therapy. Recently, some studies have suggested that the treatment with benzodiazepines could have different efficacy in depressed patients as opposed to non-depressed ones. In order to clarify the matter, some studies are currently underway, regarding the drug metabolism in rats. In order to obtain a more complete and significative set of data, the main diazepam metabolites have also been considered, namely: nordiazepam, temazepam and oxazepam, which are the demethylated, hydroxylated and demethylated hydroxylated analogues of diazepam, respectively. All of these compounds are pharmacologically active, have a long half-life and thus significantly contribute to the therapeutic effects of diazepam administration. Their determination can also give important insight into the respective balance of different metabolic pathways. Following our recent studies on benzodiazepine determination, we are developing a feasible and reliable HPLC method for the simultaneous determination of diazepam and its three main metabolites in rat brain and plasma. The method will be applied to \u201cnormal\u201d rats and to genetic rat models of depression in order to estimate the drug metabolism in the different breeds. Analyte separation was achieved on a C8 reversed phase column using an acidic phosphate buffer / acetonitrile mixture as the mobile phase. The detection wavelength is 238 nm. An accurate and innovative sample pre-treatment, based on microextraction by packed sorbent (MEPS) was developed in order to suitably eliminate endogenous interferences, using only 250 \ub5L of matrix (brain homogenate or plasma) for a complete analysis. The analytes are eluted from the cartridge with methanol; the eluate is then dried under vacuum and redissolved in the mobile phase. The results obtained with the MEPS procedure were confirmed by comparison with those obtained with a solid-phase extraction (SPE) procedure. The method has been validated with good results in terms of precision, extraction yield, accuracy, sensitivity and selectivity on both matrices and the determination of diazepam and metabolite levels in rats is currently under way. The results obtained until now are satisfactory form an analytical point of view and will hopefully contribute to the clarification of some metabolic differences between depressed and non-depressed subjects with respect to benzodiazepine biotransformation