IPICT - An Explanatory Scheme About The Innovation Phenomena Towards Integrated Care Enhanced By Digital Technologies

The introduction of innovative models of care, especially in the management of chronic diseases and other long-term conditions, responds to an urgent need of economic sustainability of the health and social system, while maintaining or increasing the level of quality of the system. In this context it is crucial to assure the proper co-evolution of organizational models and technological solutions. This paper presents an explanatory scheme about Innovation Phenomena towards Integrated Care enhanced by digital Technologies (IPICT), developed in the context of the European project STOPandGO: organisational and informational integration may be achieved both vertically among care settings and horizontally between healthcare and social care. Full integration may be the final goal of a long process made by a progressive local deployment of several initiatives, possibly coherent with regional or national plans. Within each initiative, innovation has not to be necessarily present in each individual activity or in each technological component, but it may be triggered by the appropriate combination of activities and technologies according a suitable model of care. The proposed scheme identifies six layers, ranging from a technological approach on enabling infrastructures in Layers L1 and L2, to a perspective on organizational models co-designed with technological solutions in Layers L3 and L4, up to the comprehensive vision of the overall (regional) strategies on Integrated Care in Layers L5 and L6. In particular, Layer L4 regards the measures able to “reify the innovation” in the models of care deployed within the initiatives of Layer L5. The list of L4 measures worked out by STOPandGO project was tested on the production of a coherent set of local tenders to improve the health and well-being of citizens across hetero-geneous organisational/clinical circumstances

Circ-ZNF609 regulates G1-S progression in rhabdomyosarcoma

Circular RNAs (circRNAs) represent a class of covalently closed RNAs, derived from non-canonical splicing events, which are expressed in all eukaryotes and often conserved among different species. We previously showed that the circRNA originating from the ZNF609 locus (circ-ZNF609) acts as a crucial regulator of human primary myoblast growth: indeed, the downregulation of the circRNA, and not of its linear counterpart, strongly reduced the proliferation rate of in vitro cultured myoblasts. To deepen our knowledge about circ-ZNF609 role in cell cycle regulation, we studied its expression and function in rhabdomyosarcoma (RMS), a pediatric skeletal muscle malignancy. We found that circ-ZNF609 is upregulated in biopsies from the two major RMS subtypes, embryonal (ERMS) and alveolar (ARMS). Moreover, we discovered that in an ERMS-derived cell line circ-ZNF609 knock-down induced a specific block at the G1-S transition, a strong decrease of p-Akt protein level and an alteration of the pRb/Rb ratio. Regarding p-Akt, we were able to show that circ-ZNF609 acts by counteracting p-Akt proteasome-dependent degradation, thus working as a new regulator of cell proliferation-related pathways. As opposed to ERMS-derived cells, the circRNA depletion had no cell cycle effects in ARMS-derived cells. Since in these cells the p53 gene resulted downregulated, with a concomitant upregulation of its cell cycle-related target genes, we suggest that this could account for the lack of circ-ZNF609 effect in ARMS

Circ-ZNF609 Is a Circular RNA that Can Be Translated and Functions in Myogenesis

Circular RNAs (circRNAs) constitute a family of transcripts with unique structures and still largely unknown functions. Their biogenesis, which proceeds via a back-splicing reaction, is fairly well characterized, whereas their role in the modulation of physiologically relevant processes is still unclear. Here we performed expression profiling of circRNAs during in vitro differentiation of murine and human myoblasts, and we identified conserved species regulated in myogenesis and altered in Duchenne muscular dystrophy. A high-content functional genomic screen allowed the study of their functional role in muscle differentiation. One of them, circ-ZNF609, resulted in specifically controlling myoblast proliferation. Circ-ZNF609 contains an open reading frame spanning from the start codon, in common with the linear transcript, and terminating at an in-frame STOP codon, created upon circularization. Circ-ZNF609 is associated with heavy polysomes, and it is translated into a protein in a splicing-dependent and cap-independent manner, providing an example of a protein-coding circRNA in eukaryotes

[Patterns of experienced and anticipated discrimination in patients with schizophremia. Italian results from the INDIGO international multisite project]

To describe patterns of experienced and anticipated discrimination in a sample of schizophrenic patients recruited in Italy in the context of the International Study of Discrimination and Stigma Outcomes (INDIGO)

Grotta Lu Bissu (PU 141), hot spot della biospeleologia italiana

ItSi riassumono le principali conoscenze biospeleologiche sulla grotta Lu Bissu (= L’abisso) (Pu 141), nel territorio di Castro (Lecce). Nonostante le non eccezionali dimensioni, la grotta rappresenta, dal punto di vista biologico, una delle più importanti cavità del territorio regionale, dato che al suo interno sono state rinvenute ben 15 specie troglobie (10 acquatiche e 5 terrestri), che rappresentano il 35% dell’intero popolamento ipogeo pugliese. Dopo una descrizione dei principali caratteri geologici e morfologici della cavità, si elencano le specie ritrovate nella grotta, evidenziando la necessità di una maggiore protezione della stessa, al fine della salvaguardia del notevole patrimonio biospeleologico della cavità.EnThe present paper deals with the main biospeleological outcomes from the cave Lu Bissu (= The abyss) (number 141 in the Regional Inventory of Caves), located in the territory of Castro (Lecce province). Notwithstanding its quite limited size and depth, the cave is one of the most remarkable example in Apulia as regards biospeleology: in fact, Lu Bissu hosts 15 troglobian species (10 aquatic and 5 terrestrian). They represent 35 % of the whole hypogean fauna in Apulia, which means that one third of the Apulian species are present in this small cave. After a description of the main geological and morphological characters of the cavity, the 15 species are listed and briefly described. Eventually, some considerations on the necessity to protect the cave are presented, aimed at safeguarding the important biological heritage hosted in the cave

Role of R5 phenotypic variation in mother-to-child transmission of HIV-1

chronic viral infections transmitted to infants: from mechanisms to prevention and care Meetin

The LITIS Conceptual Framework: Measuring eHealth Readiness and Adoption dynamics across the Healthcare Organizations

The Italian Federation of Healthcare Trusts and Municipalities promoted a national initiative, named LITIS, on the levels of technological innovation in healthcare, to assist its members in the governance of the eHealth phenomenon. The result is a toolkit (i) to compare the policies among HealthCare Organizations (HCOs) within a jurisdiction; (ii) to help negotiate and monitor the balanced evolution of eHealth solutions within and across the HCOs, and (iii) to facilitate the collaboration among HCOs to face common topics. The primary achievement is a Conceptual Framework, spanning over the complete spectrum of the support to care and administrative processes, assuming two perspectives: the Functions F (services for citizens, social/ healthcare professionals, managers, administrative staff) and the Enabling Components C (prerequisites to deploy the Functions and handle the change). The framework entails a taxonomy of indicators to assess the eHealth readiness and adoption in the HCOs: at first the raw data – from a survey that involved nearly two thirds of the Italian HCOs—were transformed to yield a lower layer of 145 micro-indicators, then the micro-indicators were aggregated at an intermediate layer for two different purposes, either as 36 topics or as 12 sectors; the upmost layer was made of 3 macro-area indexes and a global index, named “ICLI”. The ontological structure behind the framework allows to adapt the set of microindicators to the context of any particular jurisdiction. The global index was used to classify each HCO into one out of five “Classes of Innovation” of increasing functional completeness. The lessons learned on presentation and interpretation of results are described

Generic substitution of antidiabetic drugs in the elderly does not affect adherence

Introduction. The possibility that variation in packaging and pill appearance may reduce adherence is a reason for concern, especially for chronic diseases. The objectives of the study were to quantify the extent of switches between generic antidiabetics and to verify whether switching between different products of the same substance affects adherence. Materials and methods. All elderly residents of the Umbria Region who received at least 2 prescriptions of antidiabetics in 2010 and 2011 were included in the study. Switching was defined as the dispensing of two different products of the same substance in a series of two prescriptions. Single and multiple switchers were identified according to the num-ber of switches during 2011. Switching relevant to the three off-patent substances with generic use ≥ 5% (metformin, gliclazide and repaglinide) was quantified. The effect of switching on adherence, defined as the proportion of days in 2011 covered by prescrip-tions (Medication Possession Ratio, MPR), was estimated.Results. Among the 15 964 patients receiving antidiabetics (14.4% of the elderly popu-lation) 9211 were prescribed at least one of the generic substances. Of these patients, 23.3% experienced a single switch and 15.7% were multiple switchers (61.0% never switched). The proportion of multiple switchers increased with the number of prescrip-tions, reaching 26% among patients with ≥ 11 prescriptions. MPR was 62%, 62% and 72%, respectively among non-switchers, single and multiple switchers.Conclusions. In elderly patients treated with antidiabetics, the substitution between branded and unbranded products (as well as between generics) of the same substance, did not negatively affect adherence

Modulation of circRNA Metabolism by m6A Modification

N6-methyladenosine (m6A) is an RNA modification well-known for its contribution to different processes controlling RNA metabolism, including splicing, stability, and translation of mRNA. Conversely, the role of m6A on the biogenesis and function of circular RNAs (circRNAs) has yet to be addressed. circRNAs belong to a class of covalently closed transcripts produced via a back-splicing reaction whereby a downstream 5' splice donor site fuses to an upstream 3' splice acceptor site. Starting from circ-ZNF609 as a study case, we discover that specific m6As control its accumulation and that METTL3 and YTHDC1 are required to direct the back-splicing reaction. This feature is shared with other circRNAs because we find a significant direct correlation among METTL3 requirement, YTHDC1 binding, and the ability of m6A exons to undergo back-splicing. Finally, because circ-ZNF609 displays the ability to be translated, we show that m6A modifications, through recognition by YTHDF3 and eIF4G2, modulate its translation

484. Preclinical Proof of Concept of Transcriptional Silencing and Replacement Strategy for Treatment of Retinitis Pigmentosa Due To RHODOPSIN Mutations

Silencing and replacement strategy is a promising approach to overcome mutational heterogeneity of genetic defects. In autosomal dominant retinitis pigmentosa (adRP) due to rhodopsin gene (RHO) approximately 200 different mutations have been described, posing a challenge for the design of effective therapeutics.We designed a silencing and replacement strategy based on transcriptional silencing through an artificial zinc finger DNA-binding protein lacking effector domains (ZF6DBD), and tested both efficacy and safety in two animal models.In a murine model of adRP, we show that AAV-mediate retinal delivery (AAV2/8-CMV-ZF6-DBD) is associated with selective transcriptional silencing of the human mutated allele resulting in morphological and functional (Electroretinography, ERG a-wave and b-wave responses) rescue. We then tested the effect of transcriptional silencing in the porcine large pre-clinical model. Delivery of a low dose (AAV2/8-CMV-ZF6-DBD, 1×10e10 vector genomes, vg) of the ZF6 transcriptional silencer to the porcine retina resulted in robust transcriptional silencing of the endogenous porcine RHO transcript. Cell sorting of transduced photoreceptors showed an almost complete RHO transcriptional silencing effect (90% RHO transcriptional repression), underscoring the potency of the system. To determine the safety of the zinc-finger silencer we performed extensive RNA-seq analysis on treated and control retinae. The data sets generated demonstrate selective RHO gene transcriptional repression and a remarkably low number of differential expressed genes (DEGs), supporting specificity and thus, safety. The co-administration to the porcine retina of the AAV-ZF6 silencer (AAV2/8-CMV-ZF6-DBD) and the AAV-RHO replacement (5×10e11 vg, AAV2/8-GNAT1-HumanRHO) constructs resulted in a balanced silencing and replacement effect. This data support the use of zinc-finger based RHO transcriptional silencing for the development of a clinical trial for adRP patients