Stuttering is a neurodevelopmental disorder that typically emerges in childhood and may persist into adulthood. The current study hypothesized that adults with persistent stuttering who received active anodal transcranial direct current stimulation (tDCS) over the left inferior frontal gyrus would demonstrate significantly greater improvements in speech fluency compared to those who received sham stimulation.

A randomized, double-blind, sham-controlled clinical trial was conducted to evaluate the efficacy of a combined therapeutic approach. Thirty adults diagnosed with moderate to severe stuttering (6 females, 24 males; M = 30.60 years, SD = 10.15) were randomly assigned to either an anodal tDCS group or a sham stimulation group. Participants in the anodal group received fluency shaping therapy concurrently with anodal transcranial direct current stimulation (2 mA), while those in the sham group underwent the same behavioral therapy alongside sham stimulation. The tDCS was targeted over the left inferior frontal gyrus. Each participant completed ten 20-minute sessions over five consecutive days. Speech fluency outcomes were measured pre- and post-intervention.

The anodal tDCS group demonstrated significantly greater reductions in %SS, NAT, and SR compared to the sham group across all post-intervention time points (p < .05). Regarding the OASES, no significant between-group differences were observed at any time point; however, both groups demonstrated significant within-group improvements from baseline to the 3-month follow-up.

These findings suggest that tDCS, when combined with behavioral fluency interventions, can enhance speech fluency in adults who stutter. tDCS may therefore serve as a promising adjunctive technique to augment the effectiveness of conventional fluency therapies.

Physical inactivity constitutes a pressing societal problem. To realize physical activity's (PA) potential as a key health resource, mechanisms of PA engagement need to be understood. Laboratory and interventional studies documented that exercise relates to affective well-being (AWB) and suggested that AWB may shape PA behaviour. Digitalization enabled the investigation of how PA relates to AWB in everyday life, but findings from individual studies are ambiguous. Here we compiled 67 datasets (55.2% of eligible records) including 321,345 smartphone-based AWB ratings and nearly 1,000,000 h of accelerometer-measured PA (N = 8,223 participants) until December 2023 to clarify the nature and extent of PA-AWB associations. One- and two-stage individual participant data meta-analyses reveal that momentary AWB is associated with both prior (within, r = 0.05, 99.2% confidence intervals (CI) 0.03 to 0.06; between, r = 0.08, 99.2% CI 0.04 to 0.12) and subsequent (within, r = 0.04, 99.2% CI 0.03 to 0.05; between, r = 0.08, 99.2% CI 0.04 to 0.13) short-term PA in everyday life. Within persons, PA displays a positive association with energetic arousal, positive affective states and valence, yet a negative relation to calmness. The practical effect sizes are comparable to other daily life activities, with energetic arousal evincing the strongest relation to PA. Considerable heterogeneity in associations across individuals can be partially explained by sociodemographic moderators. Between participants, PA relates to positive affective states. The results document the critical relevance of PA-AWB relations in everyday life. They can contribute to the revision and development of health behaviour models and establish a starting point to approach behavioural, physiological and neuronal mechanisms underlying PA-AWB associations.

Keratoconus is an ectatic corneal disorder, which requires regular monitoring for early detection of progression and prompt treatment with collagen cross-linking (CXL) to stabilise the condition. This conflicts with the demand on corneal specialists to review acute referrals into the corneal service, delaying diagnosis and treatment. In this study, we examined the outcomes of an Allied Health Professional (AHP)-led keratoconus service for routine workup, monitoring, performing CXL and follow-up thereafter.

Refraction, topography and CXL operative details were taken from electronic patient records. Statistical analysis was performed in R^® (R Foundation for Statistical Computing, Vienna, Austria). 82 eyes had CXL performed by a nurse practitioner (NP) and 42 eyes by ophthalmologists. Pre- and post-operative evaluation were done by optometrists.

In total, 271 eyes of 177 patients were included. 92 patients (128 eyes) were consented and underwent CXL. 85 patients (143 eyes) where CXL was not indicated, were monitored routinely. All patients had baseline refraction and topography. Patients were reviewed at 12 and 24 months. All had topography at every visit. 71/72 eyes (98.61%) had refraction at 12 months and 57/58 eyes (91.28%) had refraction at 24 months. Patients who were operated on by NP found improvements in visual acuity at 12 months and 24 months (p < 0.05, Mann-Whitney U Test).

The AHP-led keratoconus service delivered satisfactory outcomes and can be an efficient means of dealing with these patients, complementing specialist corneal services in the NHS.

Medical assistance in dying (MAiD) is gaining legal and social acceptance; yet it remains ethically controversial and challenging for healthcare professionals. This functional MRI study examines how social norms and empathy influence MAiD decisions in 59 Australian medical students while evaluating hypothetical assisted-dying scenarios. Participants' decisions generally aligned with the legal framework. MAiD was approved when eligibility criteria were met (normative cases) and denied when they were not (nonnormative cases). Nonnormative scenarios elicited greater activation in frontoparietal brain regions involved in response selection and inhibition, consistent with increased decision difficulty. These scenarios elicited heightened activity in the precuneus, temporoparietal junction, and angular gyrus, along with stronger functional connectivity between the anterior hippocampus and the precuneus, suggesting greater reliance on memory retrieval and mentalizing. Normative scenarios were associated with increased amygdala activity, particularly among less religious participants, suggesting a role for negative affective salience. Greater activity in the ventromedial prefrontal cortex, and connectivity between the anterior cingulate cortex and this region, suggest positive feelings related to compassion when a clinician can legally approve an assisted dying request. Normative scenarios were also associated with reduced connectivity between the anterior cingulate cortex and the anterior insula, particularly in those with higher trait affective empathy, suggesting that doctors might feel a reduction in their patients' pain. The findings provide the first empirical evidence of the neural mechanisms underlying decision-making in bioethical cases involving death as the outcome, highlighting distinct contributions and potential risk factors for medical practitioners in normative and nonnormative MAiD clinical situations.

Memory destabilization is a critical phase in memory reconsolidation, during which the transient disruption of consolidated memory traces allows for the incorporation of new information, supporting memory updating and adaptive behavioral modification. While neurotransmitter release and receptor signaling during memory reactivation are known to trigger memory destabilization, the underlying regulatory networks and dynamic interactions remain unclear. Existing studies often examine neurotransmitters in isolation, lacking a unified framework. This review introduces a novel integrative framework that organizes existing evidence on neurotransmitter-mediated memory destabilization around novelty and prediction error (PE) signaling. By synthesizing experimental findings across dopamine (DA), norepinephrine (NE), acetylcholine (ACh), the glutamatergic/GABAergic systems, and the endocannabinoid system, we analyze how PE and novelty engage distinct yet interacting neural pathways. Integrating experimental data and theoretical concepts from multiple systems, we propose the PE-Novelty-Neurotransmitter Network-a unified framework explaining how multimodal neurotransmitter co-release across the midbrain-locus coeruleus-cortex circuit dynamically regulates the balance between memory stability and flexibility. This review addresses diverse memory types, with a focus on maladaptive memories, while also discussing emotional and nonemotional memories. It further discusses potential clinical implications, particularly how neuromodulatory process related to PE and novelty may inform strategies for modifying maladaptive memories and enhancing cognitive flexibility. By bridging mechanistic insights with translational considerations, this work establishes a unified framework for understanding memory plasticity and informs future efforts to translate basic neuroscience into therapeutic contexts.

Adolescent and young adult (AYA) survivors of childhood cancer face complex challenges during the transition to adult-oriented cancer care, highlighting the importance of identifying facilitators and inhibitors of transition readiness. This study aimed to identify the determinants of transition readiness among AYA survivors of childhood cancer.

This study employed a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Literature searches were conducted in MEDLINE, Scopus, CINAHL, ScienceDirect, and Wiley between December 15 and 31, 2025. Eligible studies were full-text English-language articles published between January 2015 and December 2025 that involved AYA childhood cancer survivors aged 15-39 years. Data were synthesized narratively using an inductive approach to identify key themes within the framework of Meleis' Transition Theory.

A total of 17 studies from eight countries were included. Determinants of transition readiness were grouped into three transition conditions: personal, community, and societal factors. Personal factors included beliefs and attitudes, socioeconomic status, preparation and knowledge, mental and psychological health, and clinical and sociodemographic characteristics. Community factors included relationships with healthcare providers, family and peer support, communication and shared decision-making, and community resources and services. Societal factors reflected the influence of the healthcare system, continuity and coordination of care, policy and insurance, and geographic context.

Transition readiness is shaped by multidimensional determinants that interact at the personal, community, and societal levels.

These findings underscore the need for a multidimensional, integrated approach to planning and implementing healthcare transitions from pediatric to adult care for AYA survivors of childhood cancer. They highlight key factors influencing transition readiness. For healthcare professionals, these findings provide an evidence-based foundation to deliver comprehensive, age-appropriate transitional care. For researchers, this synthesis identifies critical knowledge gaps, refines theoretical and measurement frameworks, and guides the development and evaluation of targeted transition interventions.

Brain-derived neurotrophic factor (BDNF) has been proposed as a potential biological correlate of repetitive transcranial magnetic stimulation (rTMS). However, its relationship with clinical and cognitive outcomes in mood disorders remains unclear. In this prospective exploratory pre-post study, 28 adults with major depressive disorder or bipolar disorder underwent 12 sessions of high-frequency left dorsolateral prefrontal cortex (DLPFC) rTMS while continuing pharmacological treatment. Assessments included Hamilton Rating Scale for Depression (HDRS-24), Wisconsin Card Sorting Test (WCST), plasma BDNF, and baseline glymphatic efficiency (diffusion tensor image analysis along the perivascular space (DTI-ALPS)). Over the study period, HDRS-24 scores and WCST perseverative errors decreased, whereas the number of WCST categories completed did not significantly change at the group level; peripheral plasma BDNF also increased. Greater BDNF change ratios were associated with higher baseline ALPS indices and with individual variability in WCST categories completed, but not with changes in depressive symptoms or perseverative errors. Given the uncontrolled design, these longitudinal changes should be interpreted as associations observed over time rather than treatment effects attributable to rTMS. Baseline glymphatic efficiency may therefore reflect an individual biological characteristic associated with neurotrophic responsiveness to rTMS. These exploratory findings require replication in larger controlled studies using standard clinical protocols.

Despite its clinical significance, pharmacological treatment options for alcohol use disorder (AUD) remained limited, which highlights the need for novel therapeutic targets. The ghrelin system has emerged as an important regulator of alcohol craving and intake. Liver-expressed antimicrobial peptide 2 (LEAP2) has recently been identified as an endogenous ghrelin receptor (GHSR) antagonist that influences metabolic and reward-related pathways.

As a secondary analysis of five different clinical trials, we measured LEAP2 concentrations in the collected blood samples and examined their association with alcohol craving and the effects of both acute and chronic alcohol use on LEAP2. In addition, we complemented these clinical trial analyses by conducting preclinical experiments in wild-type and GHSR-KO Wistar rats to investigate the effects of alcohol and ghrelin on LEAP2 concentrations.

In humans, LEAP2 concentrations negatively correlated with both priming- and cue-induced alcohol craving. Acute alcohol administration reduced LEAP2 concentrations 90min after oral alcohol intake, a response that was attenuated by co-administration of the GHSR inverse agonist PF-5190457. An intraperitoneal alcohol administration after a pre-treatment with ghrelin reduced LEAP2 concentrations in wild-type but not GHSR-KO Wistar rats. In contrast to acute alcohol administration, LEAP2 concentrations did not differ between people with alcohol use disorder and healthy controls and were unaffected by evidence of hepatocyte injury and alcohol abstinence.

These results enhance our understanding of the ghrelin system, particularly LEAP2, with regard to alcohol craving and consumption. This work may inform the development of novel interventions for alcohol use disorder.

The UK Medical Research Council's Guidance on Developing and Evaluating Complex Interventions (MRC GDECI) outlines a 4-phase framework for structuring research programs on interventions: development, feasibility, evaluation, and implementation. However, it provides limited practical direction on how researchers should select which phases to conduct or determine when and whether to progress between phases. This gap is particularly challenging in the context of digital health interventions (DHIs), given their fast-paced and rapidly evolving nature.

This scoping review examined the research phases conducted, how researchers progressed through them, and the intervention characteristics associated with overall program structure and duration in DHI research, to inform the design of future research programs.

We searched PubMed, Embase, CINAHL, PsycINFO, and ClinicalTrials.gov to identify complex DHIs promoting health among adolescents and young adults, implemented between 2017 and 2026, for which at least 2 phases of the MRC GDECI were reported, including the evaluation phase. For each eligible intervention, all related protocols, preprints, and published articles were retrieved to reconstruct the full research program. For each program, we analyzed the presence of each research phase, its organization (ie, phase arrangements), and the mechanisms guiding progression between phases (ie, progression mechanisms). Phase-specific and overall program durations were recorded.

A total of 31 research programs, covering 31 interventions and reported in 130 articles, were included. Development, feasibility, evaluation, and implementation phases were reported in 26, 23, 31, and 7 research programs, respectively. Three types of phase arrangements were identified: sequential, iterative, and overlapping. Progression mechanisms between phases included automatic progression, conditional progression based on researchers' appraisal of findings without prespecified criteria, and progression based on predefined quantitative criteria. Six main research program structures were observed, combining phase arrangements and progression mechanisms. Iterative arrangements were most common, observed in 22 research programs, followed by overlapping (n=10) and strictly sequential structures (n=7). Most progressions relied on researchers' appraisal of findings without prespecified criteria. Justifications for phase iteration, omission, or progression decisions were rarely reported. The median program duration was 5.8 (IQR 3.8-6.6) years (n=13). Based on these findings, a novel 4-step operational framework and visualization tools were developed to guide the design and planning of DHIs, highlighting key considerations for each step, as well as the strengths, limitations, and risks associated with each phase arrangement and progression mechanism.

This scoping review is the first to systematically examine phase arrangements and progression mechanisms in DHI research programs. Beyond descriptive reporting, it provides a conceptualization of research program structures and offers a flexible operational framework to support the concrete implementation of the MRC GDECI. Greater explicitness in decisions about program structure may enhance methodological rigor, reduce research waste, and improve the integrity and reproducibility of interventions.

PROSPERO CRD42023401979; https://tinyurl.com/mvc265y3.

Cultural competency and awareness are imperative to building trust and relationships between tribal members and non-native health care providers. The Chippewa Cree leaders in Northern Montana and Duke University School of Nursing (DUSON) collaborated to establish a service-learning opportunity focused on providing a children's summer day-camp, Camp Mi-yo-mah-chi-wi-n ("to be well"). The purpose of this project was to assess cultural competency among graduate nursing students, identify evidence-based curriculums for future academic-community activities, and demonstrate a mutually agreed on mental health model for future camps.

Eleven graduate nursing students and Chippewa Cree volunteers participated in a two-group, post-camp experience survey and key informant session at the conclusion of the initial youth camp.

The results indicated a positive and meaningful camp experience among all participants, indicating that the academic-community partnership should be cultivated and sustained. Graduate nursing student participants reported the need for enhanced cultural knowledge and understanding and a desire to ensure culturally competent care in collaboration with tribal volunteers.

Service learning is an effective way to fortify academic-clinical partnerships that are mutually beneficial with inclusion of student preparation emphasizing knowledge, beliefs and cultural competency.