Search

By 2000 the European Union (EU) had recognized that its innovation capacity was underperforming in comparison to similar competitors and trading partners. Although the EU has made an effort to stimulate public research and development (R&D) through policy tools like Pre-Commercial Procurement (PCP) and Public Procurement of Innovation (PPI), starting with the 2000 Lisbon strategy and continuing through the 2021 updated Guidance on Innovation Procurement, there has remained a gap in knowledge of and use of these tools, in particular within healthcare. The past decades have seen an explosion in the number and use of digital technologies across the entire spectrum of healthcare. Demand-driven R&D has lagged here, while new digital health R&D has largely been driven by the supply side in a linear fashion, which can have disappointing results. PCP and PPI could have big impacts on the development and uptake of innovative health technology. The Platform for Innovation of Procurement and Procurement of Innovation (PiPPi) project was a Horizon 2020-funded project that ran from December 2018 to May 2022 with a consortium including seven of Europe's premier research hospitals and the Catalan Agency for Health Information. To promote PCP and PPI, PiPPi established a virtual Community of Practice (CoP) that brings together all stakeholder groups to share and innovate around unmet healthcare needs. This perspective presents a brief history of PCP and PPI in Europe with a focus on digital innovation in healthcare before introducing the PiPPi project and its value proposition.

Abstract CaMK2N1 and CaMK2N2 are endogenous inhibitors of calcium/calmodulin-dependent protein kinase II (CaMKII), a key synaptic signaling molecule for learning and memory. Here, we investigated the learning and memory function of CaMK2N1 by knocking-down its expression in dorsal hippocampus of mice. We found that reduced CaMK2N1 expression does not affect contextual fear long-term memory (LTM) formation. However, we show that it impairs maintenance of established LTM, but only if retrieval occurs. CaMK2N1 knockdown prevents a decrease of threonine-286 (T286) autophosphorylation of αCaMKII and increases GluA1 levels in hippocampal synapses after retrieval of contextual fear LTM. CaMK2N1 knockdown can also increase CaMK2N2 expression, but we show that such increased expression does not affect LTM after retrieval. We also found that substantial overexpression of CaMK2N2 in dorsal hippocampus impairs LTM formation, but not LTM maintenance, suggesting that CaMKII activity is not required for LTM storage. Taken together, we propose a specific function for CaMK2N1; enabling LTM maintenance after retrieval by inhibiting T286 autophosphorylation of αCaMKII.

Personalized surgery (PS) involves virtual planning (VP) and the use of 3D printing technology to design and manufacture custom-made elements to be used during surgery. The widespread use of PS has fostered a paradigm shift in the surgical process. A recent analysis performed in our hospital—along with several studies published in the literature—showed that the extensive use of PS does not preclude the lack of standardization in the process. This means that despite the widely accepted use of this technology, standard individual roles and responsibilities have not been properly defined, and this could hinder the logistics and cost savings in the PS process. The aim of our study was to describe the method followed and the outcomes obtained for the creation of a PS service for the Oral and Maxillofacial Surgery Unit that resolves the current absence of internal structure, allows for the integration of all professionals involved and improves the efficiency and quality of the PS process. We performed a literature search on the implementation of PS techniques in tertiary hospitals and observed a lack of studies on the creation of PS units or services in such hospitals. Therefore, we believe that our work is innovative and has the potential to contribute to the implementation of PS units in other hospitals. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the pathological aggregation of the amyloid-β peptide (Aβ). Monomeric soluble Aβ can switch from helicoidal to β-sheet conformation, promoting its assembly into oligomers and subsequently to amyloid fibrils. Oligomers are highly toxic to neurons and have been reported to induce synaptic transmission impairments. The progression from oligomers to fibrils forming senile plaques is currently considered a protective mechanism to avoid the presence of the highly toxic oligomers. Protein nitration is a frequent post-translational modification under AD nitrative stress conditions. Aβ can be nitrated at tyrosine 10 (Y10) by peroxynitrite. Based on our analysis of ThT binding, Western blot and electron and atomic force microscopy, we report that Aβ nitration stabilizes soluble, highly toxic oligomers and impairs the formation of fibrils. We propose a mechanism by which fibril elongation is interrupted upon Y10 nitration: Nitration disrupts fibril-forming folds by preventing H14-mediated bridging, as shown with an Aβ analog containing a single residue (H to E) replacement that mimics the behavior of nitrated Aβ related to fibril formation and neuronal toxicity. The pathophysiological role of our findings in AD was highlighted by the study of these nitrated oligomers on mouse hippocampal neurons, where an increased NMDAR-dependent toxicity of nitrated Aβ oligomers was observed. Our results show that Aβ nitrotyrosination is a post-translational modification that increases Aβ synaptotoxicity. [ABSTRACT FROM AUTHOR]

Introduction: The assessment of current technologies needs a more holistic approach to obtain accurate recommendations for decision-making. The VALues In Doing Assessments of health TEchnologies (VALIDATE) methodology considers that facts and values from all stakeholders need to be included in the scoping of an assessment to gather the comprehensive information needed for unbiased decision-making. This report aimed to explore how to properly assess the integrated care of patients with aortic valve stenosis (AVS) using the VALIDATE approach. Methods: A literature review was conducted, and 11 semi-structured interviews were performed with various hospital-based healthcare professionals (cardiac surgeon, clinical cardiologist, interventional cardiologist, anesthetist, process coordinator nurse, and others) and patients. Content analysis was used for data analysis and integration. Results: The literature review showed that the cardiology and cardiac surgery perspectives were dominant in 90 percent of the articles and present in the remaining ten percent. The perspectives of other specialties (anesthesiology, primary care, and psychology) were included in three percent of the articles and patient perspectives were included in nine percent. Interviewing and considering the perspectives of the different stakeholders involved in the care pathway identified the following indicators that should be included in the assessment care for patients with AVS: difficulties associated with late diagnosis of AVS; the need to incorporate a multidisciplinary approach in patient risk assessment; the importance of geriatric evaluations; considering patient (and family and caregiver) preferences for type of treatment; the importance of following up pharmaceutical treatment and palliative care; use of telemonitoring; and digital exclusion of patients with respect to the use of apps for prehabilitation and rehabilitation. Conclusions: The stakeholders interviewed were involved in different steps of the care pathway and had differing needs, some of which were not found in the literature. The indicators suggested for inclusion in the assessment differed according to type of stakeholder and their involvement in the care pathway. Therefore, this case study exemplifies the VALIDATE method and endorses the need for multistakeholder involvement in eliciting values when scoping the assessment of a complex technology. [ABSTRACT FROM AUTHOR]

Anxiety disorders are often associated with an inability to extinguish learned fear responses. The hypocretin/orexin system is involved in the regulation of emotional states and could also participate in the consolidation and extinction of aversive memories. Using hypocretin receptor-1 and hypocretin receptor-2 antagonists, hypocretin-1 and hypocretin-2 peptides, and hypocretin receptor-1 knockout mice, we investigated the role of the hypocretin system in cue- and context-dependent fear conditioning and extinction. Hypocretins were crucial for the consolidation of fear conditioning, and this effect was mainly observed in memories with a high emotional component. Notably, after the acquisition of fear memory, hypocretin receptor-1 blockade facilitated fear extinction, whereas hypocretin-1 administration impaired this extinction process. The extinction-facilitating effects of the hypocretin receptor-1 antagonist SB334867 were associated with increased expression of cFos in the basolateral amygdala and the infralimbic cortex. Intra-amygdala, but neither intra-infralimbic prefrontal cortex nor intra-dorsohippocampal infusion of SB334867 enhanced fear extinction. These results reveal a key role for hypocretins in the extinction of aversive memories and suggest that hypocretin receptor-1 blockade could represent a novel therapeutic target for the treatment of diseases associated with inappropriate retention of fear, such as post-traumatic stress disorder and phobias. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is characterized by the oxidative stress generated from amyloid β-peptide (Aβ) aggregates. It produces protein nitrotyrosination, after the reaction with nitric oxide to form peroxynitrite, being triosephosphate isomerase (TPI) one of the most affected proteins. TPI is a glycolytic enzyme that catalyzes the interconversion between glyceraldehyde 3-phosphate (GAP) and dihydroxyacetone phosphate (DHAP). Methylglyoxal (MG) is a by-product of TPI activity whose production is triggered when TPI is nitrotyrosinated. MG is harmful to cells because it glycates proteins. Here we found protein glycation when human neuroblastoma cells were treated with Aβ. Moreover glycation was also observed when neuroblastoma cells overexpressed mutated TPI where Tyr165 or Tyr209, the two tyrosines close to the catalytic center, were changed by Phe in order to mimic the effect of nitrotyrosination. The pathological relevance of these findings was studied by challenging cells with Aβ oligomers and MG. A significant decrease in mitochondrial transmembrane potential, one of the first apoptotic events, was obtained. Therefore, increasing concentrations of MG were assayed searching for MG effect in neuronal apoptosis. We found a decrease of the protective Bcl2 and an increase of the proapoptotic caspase-3 and Bax levels. Our results suggest that MG is triggering apoptosis in neurons and it would play a key role in AD neurodegeneration. [ABSTRACT FROM AUTHOR]