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National healthcare systems face multiple challenges, including the increasing demand for care and decreasing availability of healthcare professionals. Digital health technologies represent opportunities that offer improved efficiency, accessibility, and patient care. In this scenario, Digital Therapeutics are technological advancements to treat or alleviate a disease and deliver a medical intervention with evidence-based therapeutic impacts and regulatory approval. Digital Therapeutics are a paradigm shift for physicians, who exercise caution in terms of trust and wide usage. Digital Therapeutics represents an opportunity and a challenge in healthcare system integration. The research investigates the factors explaining physicians' acceptance of Digital Therapeutics. A research model that combines organizational mechanisms derived from Institutional Theory and rational factors derived from the Technology Acceptance model was developed. The model was tested through 107 responses from a survey distributed to the members of the leading Italian scientific society in Diabetology. Literature-based hypotheses were empirically tested through Structural Equation Modelling. The analysis confirmed the influence of Perceived Ease of Use on Perceived Usefulness and Perceived Usefulness on the Intention To Use Digital Therapeutics. Rules and norms impact Perceived Usefulness when considering the influence of the scientific society. Culture and mindset towards innovation within the hospital positively affect Perceived Ease of Use. The readiness of hospital facilities enhances the extent to which physicians perceive the ease of employing Digital Therapeutics in their daily practice. Instead, esteemed colleagues' opinions and guidelines from the scientific society reveal to physicians the value of Digital Therapeutics in patients' care pathways. Institutions should prioritize cultural, normative, and regulative aspects to accelerate physicians' endorsement of Digital Therapeutics. Findings advance the theoretical knowledge around clinicians' adoption of innovative digital health technologies, unveiling the interaction between rational and institutional factors. The results highlight practical implications for healthcare institutions and Digital Therapeutics manufacturers willing to promote their adoption., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Carrera et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The gut-brain axis is a bidirectional signaling pathway between the gastrointestinal tract and the brain; it is being studied because of its potential influence in mediating mood, anxiety, and other neuropsychiatric symptoms. Previous research examining the effects of gut microbiota on neuropsychiatric disorders suggests that gut repopulation treatments such as probiotics, microbe therapy, and fecal microbiota transplantation show promising results in treating symptoms of anxiety and depression. This study explores the use of an alternative gut repopulation treatment to fecal microbiota transplantation, known as Microbial Ecosystem Therapeutic (MET)-2, as an intervention against symptoms of depression. MET-2 is a daily, orally administered capsule containing 40 bacterial strains purified from a single healthy donor., Objective: The primary aim of this study is to assess changes in mood in people with major depression that occur pre-, post-, and during the administration of MET-2. The secondary aims are to assess changes in anxiety symptoms, blood biomarker concentrations, and the level of repopulation of healthy gut bacteria as a response to treatment., Methods: In this study, we will recruit 60 adults aged between 18 and 45 years old with major depression and randomly assign them to treatment or placebo groups. Patients in the treatment group will receive MET-2 once a day for 6 weeks, whereas patients in the placebo group will receive a matching placebo for 6 weeks. Participants will complete biweekly visits during the treatment period and a follow-up visit at 2 weeks post treatment. As a primary outcome measure, participants' mood will be assessed using the Montgomery-Asberg Depression Rating Scale. Secondary outcome measures include changes in mood, anxiety, early stress, gastrointestinal symptoms, and tolerability of MET-2 treatment using a series of clinical scales and changes in blood markers, particularly immunoglobulins (Igs; IgA, IgG, and IgM) and inflammatory markers (C-reactive protein, tumor necrosis factor-α, transforming growth factor-β, interleukin-6, and interleukin-10). Changes in the relative abundance, diversity, and level of engraftment in fecal samples will be assessed using 16S rRNA sequencing. All data will be integrated to identify biomarkers that could indicate disease state or predict improvement in depressive symptoms in response to MET-2 treatment., Results: Given the association between the gut microbiome and depression, we hypothesized that participants receiving MET-2 would experience greater improvement in depressive symptoms than those receiving placebo owing to the recolonization of the gut microbiome with healthy bacteria modulating the gut-brain axis connection., Conclusions: This study is the first of its kind to evaluate the safety and efficacy of a microbial therapy such as MET-2 in comparison with placebo for major depressive disorder. We hope that this study will also reveal the potential capabilities of microbial therapies to treat other psychiatric illnesses and mood disorders., Trial Registration: ClinicalTrials.gov NCT04602715; https://clinicaltrials.gov/ct2/show/NCT04602715., International Registered Report Identifier (irrid): DERR1-10.2196/31439., (©Arthi Chinna Meyyappan, Cassandra Sgarbossa, Gustavo Vazquez, David J Bond, Daniel J Müller, Roumen Milev. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 22.09.2021.)

Reactivated long-term memories can become labile and sensitive to modification. Memories in this destabilized state can be weakened or strengthened, but there is limited research characterizing the mechanisms underlying retrieval-induced qualitative updates (i.e., information integration). We have previously implicated cholinergic transmission in object memory destabilization. Here we present a novel rodent paradigm developed to assess the role of this cholinergic mechanism in qualitative object memory updating. The post-reactivation object memory modification (PROMM) task exposes rats to contextual information following object memory reactivation. Subsequent object exploratory performance suggests that the contextual information is integrated with the original memory in a reactivation- and time-dependent manner. This effect is blocked by interference with M 1 muscarinic receptors and several downstream signals in perirhinal cortex. These findings therefore demonstrate a hitherto unacknowledged cognitive function for acetylcholine with important implications for understanding the dynamic nature of long-term memory storage in the normal and aging brain.