Contemporary Clinical Trials Communications

ObjectivesTo investigate how nutrition readiness to change influences implementation of dietary behavior changes and to compare the gut microbiomes and document gut microbiome composition changes over time in individuals with early Alzheimers disease dementia (eAD), mild cognitive impairment (MCI), and healthy controls (HC) Overall, this study aims to add to the emerging field of how the gut microbiome influences the nervous system. MethodsThis is a sub-study of a multi-prong proof-of-concept, observational study mapping the gut microbiome: 15 HC, 15 MCI, 15 eAD (n=45). At 0-, 3-, and 6-months, participants are provided lifestyle recommendations tailored to their gut microbiome. Participants may choose to implement this or not and are observed throughout (observational intervention study). In this sub-study, a survey is developed and implemented in conjunction with dietary assessment (DietID) to evaluate the role of Readiness to Change in implementation of dietary recommendations. ResultsThis is the sub-study protocol from an ongoing parent study. DiscussionThis protocol presents a novel intervention to assess the gut microbiome, individual dietary patterns, and readiness to make lifestyle change related to diet. Trial RegistrationNCT06039267

BackgroundMore than 6.2 million people have died already from COVID-19. Drug resistance and relapse cases from first generation therapeutics calls for development of new drugs in alternative medicine. Complementary and Alternative Medicines (CAM) that include herbal remedies and phytochemicals are usually not fully integrated into mainstream healthcare systems. The study proposes a CAM remedy, a new polyherbal formulation NAOQ19 against the SARS-CoV-2. MethodsThe present study consists of invitro and invivo evaluation of NAOQ19 against SARS-CoV-2 infection. First, invitro testing of NAOQ19 anti-viral activity was carried out on three relevant cell lines: Vero E6, A549ACE2 and Huh 7.5.1 ACE2TMPRSS2. Next, animal model testing of NAOQ19 was performed in Syrian golden hamsters along with positive control Remdesivir and infection control for 3 days to determine the efficacy and safety of the formulation. Finally, a double blind randomized clinical trial with mild to moderate COVID-19 infected patients were evaluated to test the efficacy of NAOQ19 in human settings. ResultsThis study demonstrated a strong anti-viral (low EC50) activity in cell culture with live virus and exhibits reduced plaque forming units (high antiviral activity) in the Syrian golden hamster model. Moreover, in the clinical trials, NAOQ19 shows high efficacy demonstrating early recovery and reduced levels of inflammatory biomarkers among COVID-19 infected patients. ConclusionThis novel polyherbal formulation NAOQ19, demonstrates strong anti-viral activity in preclinical and clinical study; thereby proving its candidacy as a low-cost alternative medicine with minimal adverse effects.

1.This paper reports the statistical analysis plan for the AVERT-DOS trial: A Phase 3, Multi Arm, Multi Stage, Covariate Adjusted, Response Adaptive, Randomised Trial to Determine Optimal Early Mobility Training after Stroke. It contains a trial overview, regulatory information and details of the planned main analyses for the study protocol version Version 5; 15 June 2025.

Exercise training is a cornerstone of Cardiovascular Rehabilitation (CR) and, as of now, moderate-to-vigorous continuous exercise training (MICT) is the standard. New exercise modalities in the context of CR are constantly being explored to improve patient outcomes. These Canadian Association of Cardiovascular Prevention and Rehabilitation (CACPR) exercise training recommendations provide a synthesis of evidence-informed recommendations from existing documents, including recommendations around High-Intensity Interval training (HIIT). CACPR created a pan-Canadian Exercise Working Group with various knowledge users (e.g., kinesiologists/exercise physiologists, physiotherapists, cardiologists, and patients) with expertise in CR-based exercise, who developed knowledge gap questions related to exercise training based on a literature review and synthesis of all available recommendations. An independent evidence-synthesis team performed a rapid review and meta-analyses to address the questions. The working group used this data to develop relevant recommendations. The final guidelines include 12 recommendations for CR exercise, including nine from previous documents and three new recommendations based on HIIT. The previous recommendations address exercise assessments and prescriptions for CR for various patient profiles. The new recommendations suggest that HIIT can be used to improve exercise capacity in patients with coronary artery disease (CAD), heart failure (HF) or atrial fibrillation. They also state that HIIT is superior to MICT in patients with CAD, that patients with HF should be considered for either HIIT or MICT and that any HIIT interval duration can be used as part of CR. Overall, these recommendations provide guidance for exercise in Canadian CR programs.

BackgroundLong Covid, also referred to as post-acute sequelae of SARS-CoV-2 infection (PASC), is characterized by symptoms that persist or emerge weeks to months following acute COVID-19 illness. Cognitive impairments affecting attention, memory, and executive functioning--commonly described as "brain fog"--are frequently reported. Currently, limited evidence-based cognitive rehabilitation interventions specifically target these impairments. ObjectivesThis pilot randomized controlled trial aims to evaluate the feasibility and acceptability, and to develop preliminary data regarding efficacy of Attention Process Training-3 (APT-3), a computerized attention training program, for individuals with Long Covid-related brain fog. MethodsThis study uses a three-arm randomized controlled design. Participants are randomized to (1) Immediate Attention Training, (2) Delayed Attention Training, or (3) Music Activity. Participants complete comprehensive cognitive assessments at baseline, post-intervention, and one-month follow-up. The Immediate Attention Training group completes a 4-week APT-3 intervention, while the Music Activity group engages in a 4-week music-based listening activity. The Delayed Attention Training group dont receive any intervention for 4 weeks. Following completion of the final assessment, participants in the Music Activity and Delayed Attention Training groups are offered the APT-3 intervention. Feasibility and acceptability outcomes include recruitment, retention, and adherence numbers, and participant satisfaction. Preliminary data regarding efficacy will be determined using objective cognitive tests and subjective self-report measures. ConclusionsThis pilot trial will inform the feasibility and acceptability of APT-3 and generate preliminary efficacy data to guide the design of a future fully powered randomized controlled trial targeting brain fog associated with Long Covid.

BackgroundOur study aimed to investigate the relationship between phenotypic age acceleration (PAA), bowel dysfunction (constipation, diarrhea), and depression severity, and examine whether phenotypic age acceleration can play a mediating role in bowel dysfunction and depression severity. MethodsThe data analysis of our study was conducted from the National Health and Nutrition Examination Survey (2005-2010). Participants with bowel dysfunction were identified on the questionnaire of bowel health. Depression was determined based on the Patient Health Questionnaire-9 (PHQ-9). The calculation of PAA is based on 9 test indicators and actual age; a higher PAA means accelerated aging. In this study, a weighted linear regression model was used to analyze the associations among defecation disorders, PAA, and depression. Restricted Cubic Spline (RCS) curves were applied to explore the potential non-linear relationships between the aforementioned variables. Additionally, a mediation effect model was employed to verify whether PAA could function as a mediating variable in the relationship between defecation disorders and depression. ResultA total of 11,808 participants were included in this study. Linear regression analysis showed that both diarrhea ({beta}=3.73, 95% Confidence Interval (CI): 1.69-8.22, P=1.60x10-3) and depression severity ({beta}=1.08, 95%CI: 1.06-1.09, P=4.61x10-16) were positively correlated with PAA. In addition, both constipation ({beta}=2.76, 95%CI: 1.89-4.04, P=2.28x10-6) and diarrhea ({beta}=4.29, 95%CI: 2.65-6.95, P=2.11x10-7) were positively correlated with depression severity. Further mediation effect analysis revealed that PAA may play a mediating role in the association between diarrhea and depression severity (the proportion of mediation effect in the total population was 7.2285%). When exploring whether PAA exerts a mediating role in the association between constipation and depression severity, it was found that PAA played a mediating role in female participants and participants aged <60 years, except for male participants and those aged [&ge;]60 years (the proportion of mediation effect was 9.8417% in females and 8.4512% in the population aged <60 years, with all relevant P-values <0.005)

Objective: A questionnaire survey was conducted on the willingness and demand for acupuncture treatment in patients with malignant tumors, and the possible factors affecting patients' willingness and demand for acupuncture treatment were explored. Methods: A voluntary, anonymous survey was conducted between February and May 2025 among patients with malignant tumors aged 18 years and older who visited Beijing Cancer Hospital. The questionnaire included 16 questions addressing three dimensions:current medical purposes,Traditional Chinese Medicine(TCM) literacy, and acupuncture treatment needs.The questionnaire was posted online and completed by respondents using a smartphone interface. Results: A total of 511 valid questionnaires were retrieved in the survey, and 481 patients(94.1%) are willing to receive acupuncture treatment. Among the 481 patients willing to receive acupuncture treatment, the top five symptoms they hoped to improve with acupuncture were: disturbed sleep (245 participants, 50.9%); pain (229 participants, 47.6%); fatigue (177 participants, 36.8%); numbness (165 participants, 34.3%); and poor appetite (144 participants, 29.9%). Among patients who chose to "explicitly accept" acupuncture treatment and those who "accepted acupuncture treatment upon doctor's recommendation", 55% and 56% respectively had good knowledge of traditional Chinese medicine (TCM) culture. In contrast, this proportion was only 36.7% among patients who refused acupuncture treatment, and the difference was statistically significant (P<0.05). The survey results also show that Female patients reported significantly higher demands for pain relief and improved sleep than male patients, with statistically significant differences (P<0.05). Furthermore, those aged 18-45 and with better TCM literacy were more likely to desire acupuncture to improve sleep, with statistically significant differences (P<0.05). Conclusion: Differences in TCM literacy can influence patients' willingness to choose acupuncture treatment. Strengthening patient health education and improving TCM literacy will help increase cancer patients' willingness to choose TCM acupuncture treatment, thereby enabling them to benefit from acupuncture. For patients aged 18-45, those with good TCM literacy female with high acupuncture needs, acupuncture treatment may be recommended as a priority.

BackgroundCognitive impairment has significant implications for function and quality of life and is common in individuals with post-acute sequelae of SARS CoV-2, also known as long COVID (LC). Emerging evidence suggests that sustained neuroinflammation, cerebrovascular dysfunction, and mitochondrial impairment are contributors to cognitive symptoms. Microtesla Magnetic Therapy (MMT) is a low-amplitude radiofrequency magnetic field intervention that has demonstrated anti-inflammatory and neuroprotective effects in preclinical models, suggesting it may be valuable in the management of cognitive impairment from LC and other neurological disorders. This study is the first randomized controlled trial to evaluate MMT for LC-related cognitive impairment. ObjectiveTo evaluate the feasibility, safety, and preliminary efficacy of an at-home MMT intervention in individuals with moderate-to-severe cognitive impairment from LC. MethodsIn this prospective feasibility study, 30 participants with LC-related cognitive impairment were randomized (2:1) to receive active or sham MMT. Participants self-administered 15-minute treatments at home with remote monitoring twice weekly for 4 weeks using a head-worn device that delivered a nonthermal radiofrequency magnetic field to the whole brain. Feasibility was defined as completion of at least 80% of prescribed treatments and all study visits. Secondary outcomes included safety, cognitive function, and self-reported mood and quality of life assessed at baseline, post-treatment (Week 4), and follow-up (Week 8). ResultsFeasibility was high, with 100% treatment adherence among participants who completed the study and strong usability ratings for at-home administration. There were no device-related adverse events. Compared with sham, participants receiving active MMT showed significantly greater improvements from baseline to Week 8 in WAIS-IV Digit Span Sequencing (p= 0.026), HVLT-R Recall (p= 0.044), and D-KEFS Color Naming (p= 0.049). Additional measures of attention, processing speed, and executive function demonstrated favorable trends in the active group. Emotional well-being, assessed by the SF-36, improved significantly in the active group at Week 8 compared with sham (p= 0.017), and mood symptoms showed clinically meaningful improvement. ConclusionsAdministration of the MMT intervention at home was feasible, safe, and well tolerated in individuals with cognitive impairment from LC. Preliminary findings suggest sustained clinically meaningful improvements in multiple cognitive domains and mood following treatment. Trial RegistrationClinicalTrials.gov NCT06739668, https://clinicaltrials.gov/study/NCT06739668, 2024-12-17

BackgroundHwa-byung (HB) is a Korean culture-bound syndrome characterised by prolonged suppression of anger and somatic complaints. No evidence-based digital therapeutic (DTx) has been developed for HB. We evaluated the feasibility, user experience (UX), and preliminary clinical effect of an acceptance and commitment therapy (ACT)-based DTx application, Hwa-free, for HB. MethodsAdults aged 19-80 years diagnosed with HB were enrolled in a four-week app-based intervention with assessment at baseline (Week 0), Week 2, Week 4, and Week 8 follow-up. The primary outcome was UX assessed via a 22-item survey at Week 4. Secondary outcomes included HB-related symptom and personality scales, depression, anxiety, anger expression, psychological flexibility, health-related quality of life, and heart rate variability. ResultsOf 45 screened, 30 were enrolled and 28 constituted the modified intention-to-treat population. Mean app use was 19.9 {+/-} 7.9 days (71.2% adherence over 28 days). Adverse events were infrequent and unrelated to the intervention. Positive response rates exceeded 80% for video content (items 2-4: 82.8-89.7%), HB self-assessment (86.2%), meditation therapy (86.2%), and in-app guidance (85.7%). Pre-post improvements from baseline to Week 4 were observed in 11 of 18 clinical scales, including HB Symptom Scale ({Delta} = -9.8, Cohens d = -0.92), Beck Depression Inventory-II ({Delta} = -13.3, d = -1.11), and state anger ({Delta} = -7.8, d = -0.96). The HB screening-positive rate declined from 100% at baseline to 55.6% at Week 8. ConclusionsHwa-free demonstrated adequate feasibility, acceptable UX, and preliminary evidence of clinically meaningful improvement in HB-related symptoms. Future randomised controlled trial is warranted. Trial registrationCRIS, KCT0011105

The transition to higher education is characterized by increased academic demands and psychosocial stress, which may negatively affect cognitive functioning and student well-being. Executive functions (working memory, inhibitory control, and cognitive flexibility) are critical for academic adaptation and can be enhanced through structured interventions. Physical exercise, mind-body practices, and cognitive training have demonstrated potential benefits for executive functioning and stress reduction; however, few randomized controlled trials have directly compared interventions with different physical and cognitive demands in university students, particularly in Latin America. In addition, most studies have relied on self-report measures and physiological stress biomarkers such as salivary cortisol. This protocol describes a three-arm, parallel-group randomized controlled trial designed to evaluate the effects of a 12-week intervention on executive functions and stress in first-year university students. The study will recruit 120 first-year health-science students aged 18-25 years. Participants will be randomly assigned (1:1:1), using block randomization stratified by sex, to one of three interventions delivered twice weekly (24 sessions of 60 minutes): (1) moderate-to-vigorous motor-cognitive dual-task exercise (DT); (2) low-to-moderate intensity Tai Chi (TC); or (3) supervised digital cognitive stimulation (CS) using structured graphomotor tasks. Primary outcomes include executive functions assessed through standardized neuropsychological measures. Secondary outcomes include stress will be evaluated using the Academic Stress Inventory, Depression Anxiety Stress Scales and salivary cortisol collected in the morning using passive drool and analyzed by competitive ELISA.Other outcomes include physical activity levels, anthropometric and body composition measures, and handgrip strength. Data will be analyzed following an intention-to-treat approach using repeated-measures models, with multiple imputation for missing data. The study has received institutional ethics and biosafety approval. Trial registration: ClinicalTrials.gov Identifier: NCT07443904.

Structured AbstractO_ST_ABSImportanceC_ST_ABSRemote sampling technologies are invaluable for protecting both participants and researchers when studying highly infectious diseases. When leveraged for longitudinal studies, remote sampling with transcriptomic readouts is a powerful tool for studying the host immune response. Additionally, remote study flexibility circumvents common barriers to research participation including length of commute, transportation, and scheduling, thereby expanding access to clinical research. ObjectiveIn this work, we investigate the effectiveness of a remote study model for reaching women from underrepresented, underserved, and underreported (U3) populations. We sought to recruit individuals who qualify as underrepresented in clinical research, who are located in rural areas, or who come from disadvantaged backgrounds per the NIH definition. DesignIn this longitudinal study, U3 women positive for COVID-19 were enrolled and followed over the course of 6 months. In the first month of the infection, participants (n = 40) self-collected a set of 5 nasal swabs, 5 homeRNA-stabilized blood samples, and 2 additional unstabilized blood samples at first and last sampling. Sampling time points were spaced 5 days apart, so that the total of the 5 time points was completed within 25 days. homeRNA is a platform for remote self-collection of blood samples with subsequent RNA stabilization. A subset of participants likely to develop post-acute sequelae of COVID-19 (PASC) and their age-matched controls were selected to self-collect an additional set of 5 nasal swabs and 5 homeRNA-stabilized blood samples during month 3 of study participation, with the same sampling frequency. All participants were resurveyed at months 4, 5, and 6 about their symptoms. Participants also completed surveys at each sampling and a more comprehensive survey about study experience after each set of 5 time points. SettingThis was a fully remote study with all sampling supplies and instructions shipped to the participants. Participants self-collected blood and nasal swabs at home and shipped these back to our lab for further processing. Surveys were administered electronically using REDCap. ParticipantsFor this study, we enrolled women who were 18 or older, met the NIH criteria for U3, and who had tested positive for SARS-CoV-2 within a week of enrollment. Further, we excluded protected populations including individuals who were pregnant and/or incarcerated. Of the 334 individuals who completed the screening process, 65 were invited into the study based on the eligibility criteria and balancing age, race/ethnicity, and state of residence to closely correspond to the demographics of the United States. Of the 65 invited individuals, 40 were fully enrolled in the study and 39 completed all study components. Main Outcomes and MeasuresPrior to the study, we proposed that the increased flexibility of a remote study design would allow for participation of populations underrepresented in clinical research. The primary measurements planned for this study consisted of usability data and general experience in a longitudinal study. These data were collected by self report using electronically administered surveys. The Consolidated Framework for Implementation Research (CFIR), a well-established implementation science framework, was used to guide the development of questions about usability and study experience. Results40 women were recruited from 19 states, with diverse racial backgrounds (62% White, 15% Black or African American, 10% Asian, 5% American Indian or Alaska Native, 5% Other, 3% More than one race), a mostly even age distribution (26% ages 20 - 29, 15% ages 30 - 39, 31% ages 40 - 49, 28% ages 50+), and most of whom (80%) are categorized as having a disadvantaged background per the NIH. Survey responses show high satisfaction with the study, where all participants who completed the study (100%, n = 39/39) indicating that they would be willing to participate in a similar study again, with most (n = 32/39) indicating a willingness to participate for up to 4 years with around 15 samples collected per year. We note that 4 years was the longest time period that participants were able to select in their surveys, suggesting that participants may be willing to participate for even longer periods. Most (>90%) either agreed or strongly agreed that all components of the kit were easy to use. Conclusions and RelevanceThe high retention (98%, n = 39/40) and satisfaction of participants in this study indicates the utility of a remote study design for longitudinal research. We also find that study topic, flexibility of study, and positive interactions with the study team are important factors for participant recruitment and retention. This work suggests that the increased flexibility of a fully remote design enables engagement of individuals who may otherwise be excluded from clinical research.

Abstract Background: Resilience is acknowledged to be an important component for successful aging in older adults, but there is scant evidence with which to inform public health interventions for this age group. The aim of this study is to determine whether the public health intervention, mindfulness for later life is both feasible and acceptable to older adults. Methods: Participants were recruited from September 2021 to June 2022 through older adult organisations and charities, such as the University of the Third Age, Age UK, and Age Concern, and by adverts distributed through village newsletters and support organisations. Participants were offered six weekly sessions of mindfulness therapy, the program was based on the mindfulness-based stress reduction program, each session was two hours long with 10-15 participants per program. The following two pre-defined indicators of success needed to be met for the program to be deemed feasible: successful uptake (recruitment of 30 participants over nine months) and initial engagement. Results: Thirty-three potential participants were screened for eligibility over nine months, 31 of whom were recruited to the study (103% of the target sample). Of these, 28 participants (90%) completed four or more online sessions. Thus, predefined indicators of feasibility were met. Conclusions: This study supports the feasibility of delivering the mindfulness for later life program as a public health intervention, including recruitment and treatment completion. A full-scale trial to assess the clinical- and cost-effectiveness of the intervention including its long-term effects is warranted.

BackgroundMenopausal obesity is a type of obesity in women during menopause where the decline of ovarian function and the decrease of estrogen levels lead to an imbalance between energy intake and consumption in the body, resulting in fat accumulation and weight gain. Moxibustion, as a green therapy of non-interventional external treatment that prevents and treats diseases through thermal stimulation of relevant acupoints, has been widely used in clinical practice because of its simplicity, convenience, effectiveness, low price and high compliance. PurposeTo clarify the pathogenesis of menopausal obesity and the biological mechanism of moxibustion treatment for menopausal obesity. MethodsWe selected 9 plasma samples from menopausal obese patients before and after moxibustion treatment, as well as 9 plasma samples from the healthy control group. After sample mixing and replication, DIA quantitative proteomics analysis was used to screen out differentially expressed proteins, and bioinformatics analysis was conducted. ResultsThe plasma proteomic analysis revealed a significant increase in the protein expression levels of APOC2 and PZP in menopausal obesity patients. These differential proteins primarily participate in biological regulation, cell metabolism, and reproductive development processes. Their biological processes and molecular functions are mainly associated with enzyme inhibitor activity, calcium-dependent protein binding, lipid localization, and plasma lipoprotein particle assembly. The pathogenesis of menopause obesity is linked to the accumulation of visceral fat resulting from changes in sex hormone levels and reduced energy consumption following the decline of female ovarian function. Following moxibustion treatment, there was a notable down-regulation in the plasma levels of sialoglycoprotein receptor 2 (ASGR2), membranin A1 (ANXA1), and human heterogeneous nuclear ribonucleoprotein C (HNRNPC) among menopausal obesity patients. Their biological processes and molecular functions were primarily concentrated on intracellular hagy, nucleic acid binding, tissue regeneration, and neutrophil clearance. ConclusionThe mechanism underlying moxibustions effectiveness in treating menopausal obesity may involve down-regulating HNRNPC expression, activating the PI3K/Akt/mTOR autophagy signaling pathway, regulating hormone levels to delay ovarian aging thereby improving lipid metabolism.

BackgroundCognitive deficits in anxiety disorders (ADs) contribute to clinical and socio-occupational dysfunction, necessitating targeted interventions. NoveltyIntegrated Cognitive Control Training (ICCT), a novel intervention, has demonstrated benefits in other disorders, however, remains unexplored in ADs. With its process-specific training and multi-pronged exercises for stimulation, metacognitive training and generalization, it has potential for enhancing cognitive functions in ADs. ObjectivesThis paper describes the study protocol for a multi-site randomized controlled trial (RCT) to test efficacy of ICCT in individuals with ADs. MethodsAdults diagnosed with ADs (n=100) will be recruited across two sites. Following baseline assessments, they will be randomized to either ICCT (8 weekly sessions) or Treatment As Usual (TAU). ICCT will be delivered through once-weekly therapist-guided, and smartphone app-based ( Cogtrain) homework (20-30 mins, 4-6 times per week). Multimodal assessments will be carried out at baseline, mid-intervention (4 weeks), post-intervention (8 weeks) and follow-up (20-24 weeks). The primary measure comprises Hamilton Anxiety Rating Scale, with secondary measures of Work and Social Adjustment Scale (socio-occupational functioning), neuropsychological tests (attention, memory and executive functions) and functional Magnetic Resonance Imaging of the cognitive control circuits. Intervention feasibility and acceptance metrics (response rate, intervention relevance) will also be recorded. Quality assurance and ethical procedures will be documented. Expected outcomeThe ICCT is expected to enhance cognitive functioning in adults with ADs, in addition to symptom reduction, changes in underlying neural circuits of cognitive control and improve overall functioning. Digital delivery through a smartphone app may provide a cost-effective and scalable intervention, useful in resource-constrained settings. Key MessagesThis multi-site randomized controlled trial evaluates a novel, smartphone-delivered Integrated Cognitive Control Training (ICCT) program for adults with anxiety disorders, targeting core cognitive deficits that contribute to functional impairment. By combining therapist-guided sessions with app-based training and multimodal assessments, the study examines both clinical and neural outcomes. Findings are expected to inform the scalability and feasibility of process-based digital cognitive interventions for anxiety disorders, particularly in resource-limited settings. Protocol RegistrationTrial registry name: Clinical Trial Registry of India URL: https://ctri.nic.in/Clinicaltrials/************** Registration number: CTRI/202*/**/******

IntroductionThis clinical trial investigates the efficacy and safety of a personalized 15-day accelerated intermittent theta-burst stimulation (aiTBS) protocol, targeted at either the default mode network (DMN) or the fronto-parietal network (FPN), in individuals with mild Alzheimers disease (AD). Methods45 patients with mild AD were randomized 1:1:1 to receive 15 consecutive days of high-dose aiTBS (7200 pulses/day) targeting the DMN or FPN, or sham. The primary outcome was the change in ADAS-Cog after 15 days of treatment. ResultsBoth active aiTBS groups demonstrated significantly greater ADAS-Cog improvement than sham at the primary endpoint. Response rates for a clinically meaningful improvement ([&ge;]3-points on ADAS-Cog) were significantly higher in the active groups (DMN: 38%; FPN: 47%) than in the sham group (0%). The improvement in active groups was sustained at 3-month follow-up. DiscussionPersonalized aiTBS targeting the DMN or FPN produced clinically meaningful cognitive benefits in mild AD and was safe.

BackgroundAdapted dance is a promising rehabilitation intervention for physical and psychosocial impairments in people with chronic stroke. However, in-person attendance is hindered by limited community ambulation, transportation, and schedule conflicts. At-home participation with a live-streamed dance program could address these issues, but psychosocial benefits may be diminished because of reduced social interactions. The primary objective of this study was to assess the feasibility and safety of a live-streamed dance program for chronic stroke. Secondary objectives were to characterize participants who choose live-stream vs in-person options and quantify pre-post changes in balance, gait and social connection. MethodPeople with chronic stroke were given the choice of attending a live-streamed adapted dance program either in-person or at home twice a week for 4 weeks. A priori feasibility criteria were tracked, and participants were characterized with self-report (Center for Epidemiologic Studies Depression Scale; CES-D) and performance-based measures (e.g., Montreal Cognitive Assessment, Chedoke McMaster Assessment) at baseline. Pre-post measures of secondary outcomes included gait speed, Mini Balance Evaluation Systems Test (Mini-BESTest), Activities of Balance Confidence Scale (ABC), and Inclusion of Community in Self scale (ICS). Unpaired median/mean differences in baseline clinical presentation were used to compare in-person and live-stream participants. Paired median/mean differences were used to examine change in secondary outcomes with dance. ResultsInterest and enrollment rates for both groups combined were 87% and 38% respectively. Of the 13 people who enrolled, 8 chose in-person and 5 chose live-stream. In-person and live-stream attendance rates were 83% and 89% respectively, and retention rates were 80% and 75% respectively. At baseline, the in-person group had greater depressive symptoms (CES-D score, median [IQR] difference: 11.5 [-21.5, -5]), and faster mean gait speed (-25.8cm/s [-50.98, 0.006]) than the live-stream group. There were no pre-post changes in secondary outcome measures. ConclusionsA live-streamed dance intervention featuring in-class and at-home participation is safe and feasible for people with chronic stroke. These results will inform a future randomized controlled trial to investigate the effects of a live-stream dance program with a longer duration while considering how factors such as gait function and mood may relate to the choice between in-person and at-home attendance.

Improving diversity in U.S. Alzheimers disease (AD) research is a pressing need. By 2050, Hispanic and Latino Americans will comprise 30% of the population. Hispanics are 1.5 times more likely and Blacks are twice as likely to develop AD compared to Whites, yet both remain vastly underrepresented in clinical trials research. Aging and AD research mentorship of underrepresented STEM undergraduates is designed to promote entry into related professions by students committed to decreasing disparities in AD research participation and clinical care. The NIA-funded MADURA program recruited 93 students from backgrounds historically underrepresented in STEM majors and/or from NIH-defined disadvantaged backgrounds. Trainees were placed in aging/AD research labs and received weekly training and mentorship from faculty research PIs and other types of supervisors (postdoctoral researchers, graduate students, research assistant staff...) Our study examined student ratings of the program and mentor behaviors, using a program-specific survey and the Mentoring Competency Assessment-21 (MCA-21). Trainees were highly satisfied with both mentoring relationships and the overall program. Student rated MCA-21 competency areas were quite high for both P.I.s and other types of research mentors. However, there were striking differences in associations between competencies and relationship and program satisfaction, by mentor type. For PI mentors, no MCA-21 competencies were associated with relationship satisfaction, but five of six competencies were associated with relationship satisfaction for other mentor types. Similarly, no PI mentor competencies were significantly correlated with overall placement satisfaction, but all six competencies were correlated with overall placement satisfaction for other mentor types. The authors discuss the likelihood of differing student expectations of faculty PI versus other types of research mentors, recommendations for assessing role-specific student expectations (including functions primarily possible only for senior faculty PIs), and utilizing nearer-peer plus PI faculty mentors to comprehensively address the gamut of mentee needs.

BackgroundThoracic spine mobilization (TSM) has been proposed to influence autonomic nervous system (ANS) activity, yet evidence remains inconsistent and feasibility of standardised protocols is unclear. This study aimed to evaluate whether a randomized TSM protocol can be implemented successfully in healthy participants and to provide preliminary estimates of its effects on heart rate variability (HRV) and heart rate (HR). MethodsA randomized feasibility trial was conducted with healthy young adults receiving six manual therapy sessions consisting of rotational mobilizations above Th5 over 14 days. Feasibility outcomes included adherence, absence of unexpected adverse events (UAE), and practicality of autonomic data acquisition. Physiological outcomes comprised HRV parameters, high-frequency (HF), low-frequency/high-frequency ratio (LF/HF) and HR, analyzed using autoregressive (AR) and fast Fourier transform (FFT) methods. ResultsProcedural safety and methodological integrity were confirmed (no UAE; complete datasets), but feasibility was only partially achieved due to adherence shortfalls, higher attrition, and device-related delays. Physiologically, large effect sizes were observed in the intervention group: at evening assessment, HF_AR showed ES = 0.80 (p = .008); at morning assessment, HF_FFT ES = 0.72 (p = .016), HF_AR ES = 0.78 (p = .010), and LF/HF_AR ES = 0.70 (p = .021). HR remained unchanged. These findings suggest repeated TSM may modulate HRV, primarily through HF-related changes associated with vagal activity, while LF/HF interpretation remains controversial. ConclusionA randomized TSM protocol is safe and methodologically viable with logistical refinements. Preliminary evidence indicates potential vagal modulation, warranting larger trials with respiratory control, ECG-based HRV, multimodal ANS measures, and clinical populations to confirm efficacy and translational relevance.

BackgroundReactive balance training using repeated perturbations may reduce falls, however, training methods are not easily replicated or translatable to clinical settings. This study aimed to examine the effects of a novel reactive balance training program on balance recovery from laboratory induced trips and slips and fall risk factors in older people using simple and low-cost equipment. MethodsWe conducted a randomised controlled trial involving 88 older people. An intervention group (n = 43) received the ReacStep program which involved tether-release reactive stepping and intentional slips once a week for 6 weeks. Both the intervention and control (n = 45) groups received home-based strength training for 8 weeks. Blinded staff assessed reactive balance (laboratory induced falls), physical functions at baseline (week 1) and post intervention (week 8). Weekly SMS surveys ascertained falls in daily life over 12 months. ResultsBoth groups were comparable in demographics, with a mean age of 72 years (SD = 5.6). Adherence to ReacStep sessions was high (90%). There were no significant differences between groups in laboratory-assessed reactive balance falls at post-test or daily-life falls over one year (P =.19). However, at post-test, the intervention group demonstrated significant improvements in usual gait speed, maximum step length, and choice stepping reaction time compared to controls (P <.05). ConclusionsThe ReacStep program demonstrated excellent adherence, was well tolerated, and improved gait parameters required for balance recovery following postural perturbations in older people. Nevertheless, it appears this program is not sufficient to improve reactive balance against unexpected trips and slips. Key pointsO_LIThe ReacStep program is acceptable, demonstrates excellent adherence and improves gait measures in older people, potentially reducing fall risk. C_LIO_LIThe generalisability against unexpected trips, and slips, and falls in daily life may be limited. C_LIO_LIFuture research should explore more ecological perturbations while maintaining its accessibility and acceptability. C_LI

BackgroundThe one-year SINEMA trial demonstrated improved blood pressure (BP) control and reduced mortality up to 72 months after the intervention. This article aims to assess between-arm differences in mean annual cumulative BP and to explore whether the associations between cumulative BP and biofunctional outcomes differed by trial arm. MethodsPost-hoc secondary analysis of the SINEMA cluster-randomized trial, which recruited 1299 adults with stroke from 50 rural villages in Hebei, China, between 2017 and 2018. The 12-month intervention was followed by observational assessments at 72 and 84 months post-baseline. BP was measured during each face-to-face follow-up, assessed by blinded assessors at baseline, 12, 72, and 84 months. Mean annual cumulative systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP) were calculated. Biofunctional outcomes included health-related quality of life, modified Rankin Scale, activities of daily living, physical function, and cognition function. ResultsAmong 897 participants (mean age 62.7 years; 40.8% female) with complete data across all assessment, the intervention arm demonstrated significantly lower mean annual cumulative SBP (-2.2 mm Hg; 95% CI, -3.9 to -0.6), DBP (-1.6 mm Hg; 95% CI, -2.4 to -0.7), and MAP (-1.8 mm Hg; 95% CI, -2.8 to -0.8), not PP, compared with usual care. Significant associations between cumulative BP and biofunctional outcomes were observed in the control arm while not in the intervention arm. Interaction effects between trial arm and cumulative BP were significant for multiple outcomes, most prominently for cumulative SBP. ConclusionsThe one-year SINEMA intervention was associated with lower cumulative BP burden over 72-84 months but did not improve overall biofunctional outcomes. Secondary analyses revealed that the association between cumulative BP burden and biofunctional decline differed by intervention arm, suggesting cumulative BP exposure may be an important long-term risk indicator and the intervention may modify BP-outcome relationships through mechanisms requiring further investigation.