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People with autism and intellectual disabilities, much like individuals with typical development, share a fundamental right and aspiration to realise their own life projects. However, this natural pursuit is uniquely challenging for individuals with autism and intellectual disabilities due to their communication and adaptive hurdles. This growing need has prompted the development of a specific procedure for crafting life projects geared toward enhancing their quality of life. In the present work, we will describe the six key steps and the corresponding assessment, support, and verification tools essential for establishing and actualising the life project for individuals with disabilities, as conceptualised by the Italian Society of Neurodevelopmental Disorders (SIDIN). We will start by delineating diverse preference and value assessment procedures, showcasing an array of tools tailored to accommodate the distinct characteristics of adaptive and communicative functioning in individuals with disabilities. Following this, we will provide a succinct overview of support needs assessment tools. Subsequently, we will introduce the Ecological Life Balance, which serves as an integrative tool for harmonising various assessment systems. We will propose methods for defining existential goals that prioritise quality of life and suggest strategies for implementing support plans. Lastly, we will delve into the methodologies for monitoring and verifying outcomes in the final section.

The coronavirus disease 2019 (COVID-19) pandemic caused by the emergent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) threatens global public health, and there is an urgent need to develop safe and effective vaccines. Here, we report the generation and the preclinical evaluation of a novel replication-defective gorilla adenovirus-vectored vaccine encoding the pre-fusion stabilized Spike (S) protein of SARS-CoV-2. We show that our vaccine candidate, GRAd-COV2, is highly immunogenic both in mice and macaques, eliciting both functional antibodies that neutralize SARS-CoV-2 infection and block Spike protein binding to the ACE2 receptor, and a robust, T helper (Th)1-dominated cellular response. We show here that the pre-fusion stabilized Spike antigen is superior to the wild type in inducing ACE2-interfering, SARS-CoV-2-neutralizing antibodies. To face the unprecedented need for vaccine manufacturing at a massive scale, different GRAd genome deletions were compared to select the vector backbone showing the highest productivity in stirred tank bioreactors. This preliminary dataset identified GRAd-COV2 as a potential COVID-19 vaccine candidate, supporting the translation of the GRAd-COV2 vaccine in a currently ongoing phase I clinical trial (ClinicalTrials.gov: NCT04528641)., Competing Interests: Declaration of interests S. Capone, A.R., M.G., S.B., A.S., A.M.C., R.S., F.B., A. Leuzzi, E.L., G. Miselli, A.N., M.F., F.T., M.S., A.F., S. Colloca, and A.V. are employees of ReiThera Srl. A.F. and S. Colloca are also shareholders of Keires AG. A. Lahm is a consultant for ReiThera Srl. S. Colloca, A. Lahm, A.R., and A.V. are inventors of the patent application number 20183515.4, titled “Gorilla Adenovirus Nucleic Acid- and Amino Acid-Sequences, Vectors Containing Same, and Uses Thereof.” The other authors declare no competing interests., (Copyright © 2021 The American Society of Gene and Cell Therapy. All rights reserved.)

For some years, the term "project of life" has become widely used in the field of neurodevelopmental disorders, and, at the same time, it has begun to make its way in many social and health planning documents. However, beyond its relatively widespread use, this term does not yet possess an adequate and shared frame of the main underlying decision-making processes. In particular, there is a need to identify the crucial questions for orienting the choice of goals within the adolescent transition, which represents the complex hinge between childhood and adulthood. Moreover, adulthood, which is often completely devoid of culturally and socially shared references, is still critical precisely because of the lack of future direction prompts usually represented by the stages of development. In this case, the themes of quality of life functioning as a guiding compass appear pertinent and much more relevant. The present contribution is, therefore, an attempt to present, in a unitary manner, the decision-making processes and questions at the basis of a construct of "project of life" shared within the scientific and associative communities.

Supporting individuals with NDD is extremely demanding, with significant exposure to critical contexts and events, and painful ongoing experiences. Stress and burnout condition is a main concern with growing interest in research, despite the lack of consensus on theoretical explanatory models and modification standards.The paper provides an up-to-date review of risk factors and involved processes, and presents evidence-based procedures and protocols to implement effective preventive actions addressing both organizational and individual factors. The aim is to offer a global understanding of the subject and offer examples of practical plans to increase the impact on the quality of life of clients and staff members.

Gastrokine 1 (GKN1) is highly expressed in gastric tissue and is secreted into the stomach but is not expressed in gastric cancer. GKN1 belongs to the BRICHOS domain family and plays a major role in maintaining gastric mucosa integrity. We previously demonstrated that a recombinant human GKN1 protein was able to interact with the amyloid precursor protein (APP) and was endowed with an anti-amyloidogenic property because it inhibited polymerization of the Aβ(1-40) peptide released from APP upon its partial hydrolysis. Here, we report that GKN1 can act as a physiological suppressor of Aβ production in gastric cancer cells. GKN1 blocked the access of γ-secretase to APP, thereby facilitating the cleavage of APP by α- and β-secretases. GKN1 directly interacted with APP C-terminal fragments, C83 and C99. In addition, it did not affect γ-secretase activity in gastric cancer cells because it did not alter Notch1 processing. GKN1-mediated inhibition of APP processing might represent a new approach for the prevention and therapy of Alzheimer's disease (AD)., (Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)

The gastrokine 1 (GKN1) protein is important for maintaining the physiological function of the gastric mucosa. GKN1 is down-regulated in gastric tumor tissues and derived cell lines and its over-expression in gastric cancer cells induces apoptosis, suggesting a possible role for the protein as a tumor suppressor. However, the mechanism by which GKN1 is inactivated in gastric cancer remains unknown. Here, we investigated the causes of GKN1 silencing to determine if epigenetic mechanisms such as histonic modification could contribute to its down-regulation. To this end, chromatin immunoprecipitation assays for the trimethylation of histone 3 at lysine 9 (H3K9triMe) and its specific histone-lysine N-methyltransferase (SUV39H1) were performed on biopsies of normal and cancerous human gastric tissues. GKN1 down-regulation in gastric cancer tissues was shown to be associated with high levels of H3K9triMe and with the recruitment of SUV39H1 to the GKN1 promoter, suggesting the presence of an epigenetic transcriptional complex that negatively regulates GKN1 expression in gastric tumors. The inhibition of histone deacetylases with trichostatin A was also shown to increase GKN1 mRNA levels. Collectively, our results indicate that complex epigenetic machinery regulates GKN1 expression at the transcriptional level, and likely at the translational level.

Background: We aimed to ascertain if Gastrokine 1 mRNA in the sera of patients with gastric cancer might be an informative biomarker for the disease., Results: Analysis of GKN1 mRNA in serum samples from healthy individuals (n = 23) and from patients with diagnosis of gastric cancer (n = 16), performed by using absolute quantification based on standard curve method, did not show any significative statistical difference between the two unpaired group of individuals., Conclusions: Our preliminary results did not confirm GKN1 as a potential biomarker for gastric cancer.

AMP18 is a stomach-specific secreted protein expressed in normal gastric mucosa but absent in gastric cancer. AMP18 plays a major role in maintaining gastric mucosa integrity and is characterized by the presence of a BRICHOS domain consisting of about 100 amino acids, present also in several unrelated proteins, and probably endowed with a chaperon-like activity. In this work, we exploited a functional proteomic strategy to identify potential AMP18 interactors with the aim to add knowledge on its functional role within gastric cell lines and tissues. To this purpose, recombinant biotinylated AMP18 was purified and incubated with protein extract from human normal gastric mucosa by applying an affinity chromatography strategy. The interacting proteins were identified by peptide mass fingerprinting using MALDI-TOF mass spectrometry. The pool of interacting proteins contained SLC26A3, a protein expressed in the apical membrane of intestinal epithelial cells, supposed to play a critical role in Cl(-) absorption and fluid homeostasis. The interaction was also confirmed by Western blot with anti-SLC26A3 on transfected AGS cell extract following AMP18 pull-down. Furthermore, the interaction between AMP18 and SLC26A3 was also validated by confocal microscopy that showed a co-localization of both proteins at plasma membrane level. More importantly, for the first time, we showed that SLC26A3 is down-regulated in gastric cancer and that the overexpression of AMP18 in AMP-transfected gastric cancer cells up-regulated the expression of SLC26A3 both at transcriptional and translational level, the latter probably through the activation of the MAP kinases pathway. These findings strongly suggest that AMP18 might play an anti-inflammatory role in maintaining mucosal integrity also by regulating SLC26A3 level., (Copyright © 2015 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)

Gastrokine 1 (GKN1) is a stomach-specific protein important in the replenishment of the surface lumen epithelial cell layer and in maintaining mucosal integrity. A role in cell proliferation and differentiation has also been hypothesized. Despite these findings, the function(s) as well as the cellular localization of GKN1 in the cellular machinery are currently not clarified. The investigation of subcellular localization of GKN1 in gastric cancer cells can provide insights into its potential cellular roles. Subcellular fractions of gastric cancer cells (AGS) transfected with full-length GKN1 (flGKN1) or incubated with recombinant GKN1 (rGKN1) lacking the first 20 amino acids at N-terminal were analyzed by Western blot and confocal microscopy and compared with those from normal gastric tissue. Wild type GKN1 (wtGKN1) and flGKN1 were revealed in the cytoplasm and in the membrane fractions of gastric cells, whereas rGKN1 was revealed in the cytoplasmic fractions, but a high amount was detected in the membrane pellet of the AGS lysate. The cellular distribution of GKN1 was also confirmed by confocal microscopy. The purified protein was also used to highlight its possible association with actin through confocal microscopy, pelleting assay, and size-exclusion chromatography. GKN1 co-localizes with actin in normal gastric tissue, but no direct interaction was observed between the two proteins in vitro. Most likely, GKN1 indirectly participates in actin stabilization since its overexpression in gastric cancer cells strongly increases the expression of tight and adherens junction proteins., (Copyright © 2015 Elsevier GmbH. All rights reserved.)

Gastrokine 1 (GKN1) is a stomach-specific protein expressed in normal gastric tissue but absent in gastric cancer. GKN1 plays a major role in maintaining gastric mucosa integrity and is characterized by the presence of a BRICHOS domain consisting of about 100 amino acids also found in several unrelated proteins associated with major human diseases like BRI2, related to familial British and Danish dementia and surfactant protein C (SP-C), associated with respiratory distress syndrome. It was reported that recombinant BRICHOS domains from BRI2 and SP-C precursor (proSP-C) prevent fibrils formation of amyloid-beta peptide (Aβ), that is the major component of extracellular amyloid deposits in Alzheimer's disease. Here we investigated on the interaction between human recombinant GKN1 (rGKN1) and Aβ peptide (1-40) that derives from the partial hydrolysis of the amyloid precursor protein (APP). GKN1 prevented amyloid aggregation and fibrils formation by inhibiting Aβ(1-40) polymerization, as evaluated by SDS-PAGE, thioflavin-T binding assay and gel filtration experiments. Mass spectrometry showed the formation of a prevailing 1:1 complex between GKN1 and Aβ(1-40). SPR analysis of GKN1/Aβ interaction led to calculate a dissociation constant (KD) of 34 μM. Besides its interaction with Aβ(1-40), GKN1 showed also to interact with APP as evaluated by confocal microscopy and Ni-NTA pull-down. Data strongly suggest that GKN1 has anti-amyloidogenic properties thus functioning as a chaperone directed against unfolded segments and with the ability to recognize amyloidogenic polypeptides and prevent their aggregation., (Copyright © 2014 Elsevier B.V. and Société française de biochimie et biologie Moléculaire (SFBBM). All rights reserved.)

Nowadays, treatment of chronic illnesses, such as stroke, cancer, chronic heart and respiratory diseases, osteoarthritis, diabetes, and so forth, account for the largest part of expenses in western countries national health systems. Moreover, these diseases are by far the leading causes of mortality in the world, representing 60% of all deaths. Any treatment aimed at targeting them might engage an individual for a large portion of his/her life so that personal and environmental factors can play a crucial role in modulating the person's quality of life and functioning, on top of any medical cure. Anxiety, depression, and distress for examples are not rare in patients with chronic diseases. Therefore, Cognitive and Behavior Therapy research has largely contributed in the last decades in identifying and programming interventions on such aspects as real and perceived social and family support, coping abilities, locus of control, self-efficacy that might help patients living with their chronic disease. More recently, third generation Cognitive-Behavior-Therapies, such as Dialectical Behavioral Therapy (DBT), Mindfulness Based Cognitive Therapy (MBCT), Functional Analytic Psychotherapy (FAP) and Acceptance, and Commitment Therapy (ACT) focused their attention and research efforts on developing intervention models targeting the needs of patients with a chronic disease. This paper has three aims. First is to briefly introduce ACT epistemological (Functional Contextualism) and theoretical (Relational Frame Theory) foundations as a stand point for understanding the peculiarity of ACT as a modern form of Clinical Behavior Analysis. The second aim is to introduce ACT clinical model and its six core processes (acceptance, defusion, present moment, self as a context, values and committed action) as both accountable, in their continuum, for psychological flexibility and inflexibility. Third, to present a brief overview of studies and outcomes of ACT intervention protocols and assessment tools that have been investigated in patients with chronic physical diseases, and namely: diabetes, obesity, epilepsy, and chronic pain.