Acute effects of a ketone monoester, whey protein, or their coingestion on mTOR trafficking and protein-protein colocalization in human skeletal muscle.

We recently demonstrated that acute oral ketone monoester intake induces a stimulation of postprandial myofibrillar protein synthesis rates comparable to that elicited following the ingestion of 10 g whey protein or their coingestion. The present investigation aimed to determine the acute effects of ingesting a ketone monoester, whey protein, or their coingestion on mechanistic target of rapamycin (mTOR)-related protein-protein colocalization and intracellular trafficking in human skeletal muscle. In a randomized, double-blind, parallel group design, 36 healthy recreationally active young males (age: 24.2 ± 4.1 yr) ingested either: 1) 0.36 g·kg-1 bodyweight of the ketone monoester (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (KET), 2) 10 g whey protein (PRO), or 3) the combination of both (KET + PRO). Muscle biopsies were obtained in the overnight postabsorptive state (basal conditions), and at 120 and 300 min in the postprandial period for immunofluorescence assessment of protein translocation and colocalization of mTOR-related signaling molecules. All treatments resulted in a significant (Interaction: P < 0.0001) decrease in tuberous sclerosis complex 2 (TSC2)-Ras homolog enriched in brain (Rheb) colocalization at 120 min versus basal; however, the decrease was sustained at 300 min versus basal (P < 0.0001) only in KET + PRO. PRO and KET + PRO increased (Interaction: P < 0.0001) mTOR-Rheb colocalization at 120 min versus basal; however, KET + PRO resulted in a sustained increase in mTOR-Rheb colocalization at 300 min that was greater than KET and PRO. Treatment intake increased mTOR-wheat germ agglutinin (WGA) colocalization at 120 and 300 min (Time: P = 0.0031), suggesting translocation toward the fiber periphery. These findings demonstrate that ketone monoester intake can influence the spatial mechanisms involved in the regulation of mTORC1 in human skeletal muscle.NEW & NOTEWORTHY We explored the effects of a ketone monoester (KET), whey protein (PRO), or their coingestion (KET + PRO) on mTOR-related protein-protein colocalization and intracellular trafficking in human muscle. All treatments decreased TSC2-Rheb colocalization at 120 minutes; however, KET + PRO sustained the decrease at 300 min. Only PRO and KET + PRO increased mTOR-Rheb colocalization; however, the increase at 300 min was greater in KET + PRO. Treatment intake increased mTOR-WGA colocalization, suggesting translocation to the fiber periphery. Ketone bodies influence the spatial regulation of mTOR.

Comparing the psychological outcomes of donor and non-donor conceived people: A systematic review.

BACKGROUND: Over 70 000 donor-conceived (DC) people have been born in the UK since 1991. Little is known about their long-term psychological outcomes and no systematic review has assessed these. OBJECTIVES: To conduct a systematic review of the psychological experiences of DC people through childhood and adulthood (Prospero: CRD42021257863). SEARCH STRATEGY: Searches of Cumulative Index to Nursing and Allied Health Literature (CINHAL), the Excerpta Medica database (Embase), MEDLINE® and PsycINFO, conducted on 4 January 2024. SELECTION CRITERIA: Quantitative and qualitative studies were included if: there were five or more participants; they were peer reviewed; and any DC psychological outcomes were assessed. No limits on date, language or country were applied. DATA COLLECTION AND ANALYSIS: Double screening, selection, data extraction and quality assessment were performed, using Joanna Briggs Institute (JBI) scoring. MAIN RESULTS: Fifty studies (with 4666 DC participants), mostly from high-income anglophone countries, with heterogeneity of design, populations and outcome measures, were included. Of 19 comparative studies, 14 found no difference in outcomes between DC and non-DC people, ten found better outcomes (in health, well-being, self-esteem and emotional warmth) and six found worse outcomes (increased autism spectrum disorder and attention deficit hyperactivity disorder, addiction issues, mental illness, disruptive behaviour and identity problems). Qualitative data revealed common themes relating to identity formation, mistrust and concerns regarding genetic heritage. The evidence regarding adulthood outcomes was very limited. CONCLUSIONS: The research on DC individuals presents a nuanced picture, with most studies suggesting comparable or improved outcomes in terms of well-being and relationships, but with a notable minority indicating higher rates of mental health and identity struggles. Qualitative findings underscore common negative experiences, whereas the early disclosure of DC status appears beneficial for psychological well-being.

Can Large Language Models Replace Therapists? Evaluating Performance at Simple Cognitive Behavioral Therapy Tasks.

The advent of large language models (LLMs) such as ChatGPT has potential implications for psychological therapies such as cognitive behavioral therapy (CBT). We systematically investigated whether LLMs could recognize an unhelpful thought, examine its validity, and reframe it to a more helpful one. LLMs currently have the potential to offer reasonable suggestions for the identification and reframing of unhelpful thoughts but should not be relied on to lead CBT delivery.

Integrating insights from implementation science and behavioral economics to strengthen suicide screening strategies for pediatric populations.

Suicide is a leading cause of death for young people globally. Professional organizations such as the American Academy of Pediatrics (AAP) recommend suicide screening for every young person at every healthcare contact and these guidelines are now being implemented across the US. To optimize deployment of these guidelines, we draw on insights from two parallel fields, implementation science - or the study of how to support clinicians in providing evidence-based care within organizational constraints - and behavioral economics, which centers human decision-making. In this brief review, we offer potential barriers to suicide screening and strategies to address barriers drawing on these two literatures, illustrating how best to integrate insights from these fields for maximal impact.

A Digital Microintervention Supporting Evidence-Based Parenting Skills: Development Study Using the Agile Scrum Methodology.

BACKGROUND: Conduct disorder increases risks of educational dropout, future mental illness, and incarceration if untreated. First-line treatment of conduct disorder involves evidence-based parenting skills programs. Time-outs, a frequent tool in these programs, can be effective at improving behavior, and recent apps have been developed to aid this process. However, these apps promote the use of time-outs in inconsistent or developmentally inappropriate ways, potentially worsening behavior problems. Digital microinterventions like these apps could guide parents through high-quality time-outs in the moment, but current time-out apps lack features promoting adherence to the evidence-based best practice. Agile scrum is a respected approach in the software development industry. OBJECTIVE: We aimed to explore the feasibility of using the agile scrum approach to build a digital microintervention to help parents deliver an evidence-based time-out. METHODS: The agile scrum methodology was used. Four sprints were conducted. Figma software was used for app design and wireframing. Insights from 42 expert stakeholders were used during 3 sprint reviews. We consulted experts who were identified from councils around the Midlands region of the United Kingdom and charities through personal contacts and a snowballing approach. RESULTS: Over 4 development sprints from August 2022 to March 2023, the app was iteratively designed and refined based on consultation with a diverse group of 42 experts who shared their knowledge about the content of common parenting programs and the challenges parents commonly face. Modifications made throughout the process resulted in significant app enhancements, including tailored timer algorithms and enhanced readability, as well as an onboarding zone, mindfulness module, and pictorial information to increase inclusivity. By the end of the fourth sprint, the app was deemed ready for home use by stakeholders, demonstrating the effectiveness of our agile scrum development approach. CONCLUSIONS: We developed an app to support parents to use the evidence-based time-out technique. We recommend the agile scrum approach to create mobile health apps. Our experience highlights the valuable role that frontline health and social care professionals, particularly those working with vulnerable families, can play as experts in scrum reviews. There is a need for research to both evaluate the impact of digital microinterventions on child behavioral change and also create digital microinterventions that cater to non-English speakers and individuals who participate in parenting programs in settings outside the United Kingdom.

How can a behavioral economics lens contribute to implementation science?

BACKGROUND: Implementation science in health is an interdisciplinary field with an emphasis on supporting behavior change required when clinicians and other actors implement evidence-based practices within organizational constraints. Behavioral economics has emerged in parallel and works towards developing realistic models of how humans behave and categorizes a wide range of features of choices that can influence behavior. We argue that implementation science can be enhanced by the incorporation of approaches from behavioral economics. Main body First, we provide a general overview of implementation science and ways in which implementation science has been limited to date. Second, we review principles of behavioral economics and describe how concepts from BE have been successfully applied to healthcare including nudges deployed in the electronic health record. For example, de-implementation of low-value prescribing has been supported by changing the default in the electronic health record. We then describe what a behavioral economics lens offers to existing implementation science theories, models and frameworks, including rich and realistic models of human behavior, additional research methods such as pre-mortems and behavioral design, and low-cost and scalable implementation strategies. We argue that insights from behavioral economics can guide the design of implementation strategies and the interpretation of implementation studies. Key objections to incorporating behavioral economics are addressed, including concerns about sustainment and at what level the strategies work. CONCLUSION: Scholars should consider augmenting implementation science theories, models, and frameworks with relevant insights from behavioral economics. By drawing on these additional insights, implementation scientists have the potential to boost efforts to expand the provision and availability of high quality care.