Contemporary Clinical Trials Communications

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.

BackgroundNeonicotinoid pesticides are systemic insecticides with neurotoxic potential and environmental persistence, raising concerns about chronic low-dose exposure in humans and impacts on ecosystems. In Japan, regulatory restrictions are generally less stringent than in the European Union, yet risk perception among young adults remains underexplored. ObjectiveTo examine factors associated with university students interest in pesticide-related issues, focusing on family discussions about environmental topics, household preference for organic vegetables, agricultural experience, and depressive symptoms. MethodsWe conducted a cross-sectional questionnaire survey among 690 undergraduate students at a private university in the Tokyo metropolitan area (academic year 2024). Interest in pesticide issues was assessed on a 4-point scale and dichotomized as high (very/somewhat) vs low (not very/not at all). Explanatory variables included frequency of family discussions about environmental issues, household preference for organic vegetables, agricultural experience, the Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR-J), age, and sex. Multivariable logistic regression was used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). ResultsParticipants mean age was 20.6 (SD 4.9) years and mean QIDS-SR-J score was 6.0 (SD 4.2). Overall, 74.6% reported high interest in pesticide issues. High interest was associated with more frequent family discussions about environmental issues (aOR 2.22, 95% CI 1.50-3.30; p<0.001) and household preference for organic vegetables (aOR 1.73, 95% CI 1.14-2.62; p=0.009). Agricultural experience, depressive symptoms, age, and sex were not significantly associated. Notably, while 53.2% supported pesticide-free/organic farming, 85.5% avoided blemished (insect-damaged) vegetables and 77.1% considered pesticides necessary, suggesting an attitude-behavior gap. O_TBL View this table: org.highwire.dtl.DTLVardef@102f85dorg.highwire.dtl.DTLVardef@1ffcd45org.highwire.dtl.DTLVardef@fd88b5org.highwire.dtl.DTLVardef@11a3a26org.highwire.dtl.DTLVardef@dfb213_HPS_FORMAT_FIGEXP M_TBL O_FLOATNOTable 1.C_FLOATNO O_TABLECAPTIONParticipant characteristics and related factors (N = 690) C_TABLECAPTION C_TBL ConclusionsAmong Japanese university students, interest in pesticide issues was linked to family-level environmental discourse and household organic orientation, rather than depressive symptoms. The observed gap between pro-organic attitudes and consumer preferences underscores the need for risk communication and environmental health education that connect values to feasible purchasing behaviors.

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.

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.

BackgroundFalls among older adults are a leading cause of fractures, loss of independence, and need for long-term care. Community salons in Japan promote social participation and health activities among older adults. Hydrogen-rich water is widely used as a health product, but evidence in community settings remains limited. MethodsWe conducted a prospective observational study among 48 community-dwelling older adults attending community salons in Hiroshima City, Japan. Hydrogen-rich water was offered by the salon operators as part of routine activities; the research team did not assign participants to consume it. Participants were categorized at baseline according to their usual hydrogen-rich water consumption at the salons (consumers vs non-consumers) and followed for six months. The primary outcome was the 30-second chair stand test (CS-30). Secondary outcomes included the Timed Up and Go test (TUG), usual gait speed, one-leg stance time, and grip strength. Within-group changes and between-group differences in change scores were compared. ResultsAll 48 participants completed follow-up, and no serious adverse events were reported during the study period. The consumers group showed a greater improvement in CS-30 over six months (baseline 12.96 (SD 3.21) to follow-up 14.52 (SD 3.59); change 1.57 (SD 2.41)) compared with the non-consumers group (12.52 (SD 3.00) to 12.22 (SD 3.54); change -0.30 (SD 1.55)), with a significant between-group difference in change scores (p=0.003). The consumers group also showed a greater increase in usual gait speed (0.91 (SD 0.24) to 0.98 (SD 0.26); change 0.07 (SD 0.08)) than the non-consumers group (0.94 (SD 0.24) to 0.97 (SD 0.22); change 0.03 (SD 0.05); p=0.008). No significant between-group differences were observed for TUG (p=0.57), one-leg stance time (p=0.13), or grip strength (p=0.10). ConclusionIn community-dwelling older adults participating in community salons, routine hydrogen-rich water consumption was associated with improved lower extremity function as measured by CS-30 and gait speed. Because exposure was not randomized, residual confounding cannot be excluded, and causal inference is limited. Larger studies with stronger designs are warranted.

Fortification of human milk (HM) is essential to meet the nutritional needs of very low birthweight infants (VLBWI). Most available fortifiers are derived from cows milk, raising concerns about tolerability, immunogenicity and access in low-resource settings. LioNeo is a novel multinutrient fortifier produced exclusively from freeze-dried donor HM by a certified Human Milk Bank in Brazil. Preclinical and Phase 1 testing demonstrated safety and tolerability. This Phase 2 trial evaluated the efficacy and safety of LioNeo and assessed its non-inferiority compared to a standard hydrolysed cows milk-based fortifier. We conducted a double-blind, randomized controlled Phase 2 trial at a tertiary university hospital in Brazil. Hemodynamically stable VLBWI receiving [&ge;]100 mL/kg/day of HM were randomized 1:1 to receive either HM fortified with freeze-dried donor HM (LioNeo) or a with a commercial HM additive (HMCA). The intervention lasted 21 days. Primary outcomes were changes in z-scores for length and head circumference. Secondary outcomes included weight gain, adverse events, and serum zinc and copper levels. A total of 129 infants were enrolled. Mean changes in z-scores for length (-0.08; 95% CI -0.29 to 0.12) and head circumference (-0.07; 95% CI -0.35 to 0.21) demonstrated non-inferiority of LioNeo versus HMCA. Weight gain was comparable between groups. Serum zinc concentrations decreased significantly in both groups. Copper levels were significantly higher in the LioNeo group (p < 0.01) within normal range. Adverse events occurred at comparable rates between groups, although the absolute number of events was higher in the HMCA group. LioNeo, a human milk-based fortifier, was non-inferior to a commercial cows milk-based additive in supporting growth of VLBWI, with a comparable safety profile. It may represent a promising, locally producible, and ethically compliant alternative for fortification in resource-limited contexts. The trial was registered with the Universal Trial Number: U1111-1220-0550. Protocol version 1.

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.

Withdrawal StatementThe authors have withdrawn this manuscript because We request withdrawal as the current version is incomplete and requires additional experimental data. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.

BackgroundSedentary behavior is highly prevalent following traumatic brain injury (TBI) and compounds existing risks for cardiovascular, neurodegenerative, and affective disorders. The cognitive and behavioral sequelae of TBI, including impaired decision-making, blunted reward processing, and cognitive fatigue, create particular barriers to adopting and maintaining an active lifestyle. Despite this, effective behavior change interventions targeting physical activity in community-dwelling TBI survivors remain scarce. Here, we evaluated the feasibility, compliance, and preliminary efficacy of a 12-week remotely delivered walking intervention combining planning, behavioral reminders, and monetary micro-incentives. MethodsFifty-six adults aged 40-80 years with a mild-to-moderate TBI diagnosed between 3 months and 15 years prior were randomized to either a planning, reminders, and micro-incentives intervention (n=23) or a health advice control condition (n=25). Participants wore a Fitbit Inspire 3 continuously throughout the study. Intervention participants completed weekly phone calls to plan five 30-minute walks for the following week, received daily text message or email reminders on planned walk days, and earned small monetary incentives upon walk completion. Control participants received weekly health education calls. Feasibility was assessed through recruitment, retention, and adverse event rates. Compliance was assessed via phone call completion rates and Fitbit wear time. Efficacy outcomes included weekly walk counts, walking duration, and step counts, modeled using Poisson generalized linear mixed models and linear mixed-effects models over 12 weeks. ResultsForty-eight participants completed the study (retention rate: 84.2%), with high phone call compliance in both groups (intervention: 98.4%; control: 98.1%). Intervention participants completed significantly more walks than controls from week 1 onward (aIRR = 5.33, 95% CI: 2.27-12.5, p < 0.001), with the group difference growing over time (interaction aIRR = 1.09 per week, 95% CI: 1.01-1.17, p = 0.029). Estimated marginal means indicated that intervention participants completed 5.5 times more walks than controls at week 1, increasing to 15.5 times more by week 12. The intervention group also walked significantly longer at week 1 (b = 62.14 min, 95% CI: 1.05-123.23, p = .046), with the advantage growing over time; by week 12, intervention participants walked 5.3 times longer than controls. Similarly, the intervention group accumulated significantly more steps during walks at week 1 (b = 4,779 steps, 95% CI: 45.50-9,513.00, p = .048), accumulating 3.1 times more steps than controls by week 12. ConclusionsA remotely delivered, multicomponent walking intervention targeting planning, behavioral reminders, and micro-incentives was feasible, well-tolerated, and produced meaningful increases in walking activity in community-dwelling adults with TBI. With high retention and compliance, and consistent effects on walk counts, duration, and steps across the intervention period, these findings provide compelling support for a larger, fully powered trial.

BackgroundMild traumatic brain injury (mTBI) affects millions worldwide, with cognitive impairment substantially impacting daily functioning. Despite this burden, evidence-based non-pharmaceutical interventions remain lacking in clinical practice. Emerging evidence suggests aerobic exercise may improve post-mTBI cognition; however, the methodological limitations, particularly inadequate control groups, prevent definitive conclusions. ObjectiveThis pilot randomized controlled trial examined the feasibility and preliminary efficacy of a 12-week virtual exercise intervention for community-dwelling adults aged 18-55 years with mTBI within one year of injury. MethodsThirty-seven participants were randomized to either symptom-guided aerobic exercise or active balance control; both delivered virtually three times weekly for 30 minutes over 12 weeks. Primary outcomes assessed feasibility metrics; secondary outcomes examined cognitive function. ResultsOf enrolled participants, 75% completed the intervention with 94.2% session adherence and zero adverse events, demonstrating excellent feasibility and safety. The aerobic group demonstrated greater improvements in executive function compared to balance controls, with large effect sizes for TMT B-A difference scores in both post-intervention comparisons (Hedges g = 1.20, 95% CI [0.00, 2.41]) and Group x Time interactions (Hedges g = 1.38, 95% CI [0.27, 2.49]). Additionally, the aerobic group reported fewer sleep disturbances post intervention (g = 1.65, 95% CI [0.22, 3.09]). ConclusionThese findings establish that virtual, supervised, symptom-guided exercise interventions are feasible and safe for mTBI populations, with preliminary evidence suggesting aerobic exercise specifically benefits cognitive flexibility and sleep quality following mTBI. A fully powered randomized controlled trial is warranted to confirm these effects

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

IntroductionBronchopulmonary dysplasia (BPD) remains a major complication among extremely low gestational age (ELGA) infants, with long-term respiratory and neurodevelopmental consequences. Despite advances in neonatal care, effective therapies to prevent BPD are lacking. Mesenchymal stromal cells (MSC), particularly those derived from umbilical cord (UC-MSC), offer promise due to their pleiotropic effects. Preclinical and early-phase clinical studies have demonstrated safety and potential efficacy of MSC in neonatal lung injury. The HULC-2 trial aims to evaluate whether multiple intravenous doses of human allogenic UC-MSC can reduce mechanical ventilation duration and improve the respiratory outcome in ELGA infants at high risk of developing BPD. Methods and AnalysisHULC-2 is a multicenter, double-blind, randomized controlled Phase II trial conducted in Canadian Neonatal Intensive Care Units. ELGA infants (gestational age <28 weeks) who remain ventilator-dependent between 4-14 days of life will be randomized to receive either three weekly intravenous doses of UC-MSC (10x10^6 cells/kg/dose) or a sham procedure. The primary outcome is ventilation-free days (VFDs) at 120 days post-randomization, accounting for mortality. Secondary outcomes include cell administration safety, respiratory and neurodevelopmental outcomes, and complications of prematurity. A total of 168 participants will be enrolled to detect a clinically meaningful difference in VFDs. Ethics and DisseminationEthics approval has been obtained, and the trial is registered on ClinicalTrials.gov. Results will be disseminated via peer-reviewed publications, conferences, and public engagement platforms. Parent partners are actively involved in study design and dissemination to ensure relevance and transparency. Strengths and limitations of this studyO_LIVentilation-free day (VFD) is a clinically relevant primary outcome compared to BPD, as prolonged mechanical ventilation in preterm infants is directly associated with increased risks of mortality, neurodevelopmental impairment, and other complications, making VFDs a more sensitive and meaningful measure of both survival and recovery C_LIO_LIUse of a multiple-dose regimen and fresh cell product to optimize the cells therapeutic potential C_LIO_LICell product was tested in a large animal model of BPD C_LIO_LIParents involvement in the trial design and development to deliver meaningful research that benefits patients and increase study acceptance among parents. C_LIO_LIA sham procedure was chosen over a placebo based on parent feedback, which increased the risk of unblinding, but strategies to mitigate that risk were developed. C_LI

BackgroundThe self-management of type 2 diabetes (T2D) typically requires enacting various lifestyle changes, which can challenge people living with T2D. Clinical encounters between people with T2D and their clinicians, however, are often focused on metabolic management, leaving less time available for other self-management topics. The QBSAFE cards help patients articulate aspects of their experience with diabetes and prioritize issues for discussion. MethodsThis report details secondary outcomes of a randomized controlled trial; primary outcomes are reported elsewhere. All data was collected at Fair Haven Community Health Care, a federally qualified primary care clinic. 11 clinicians were randomly assigned to provide either usual care or usual care with QBSAFE cards to 155 of their patients with type 2 diabetes and hemoglobin A1c >8%. All patient encounters were video recorded for analysis. Patients and clinicians were not blinded to arm allocation but were kept unaware of the specific aims of the trial. Encounter video reviewers were blinded to arm allocation, but not to specific aims of the trial. The outcomes of interest for this report were the extent to which the QBSAFE cards were used as intended, their effect on the topics of discussion, and whether they enabled clinicians to notice and respond to each patients situation; comparisons between arms were conducted by a linear mixed model with fixed effect of arm and cluster effect of clinician, analyzed in both intent-to-treat and per-protocol populations. Findings12 patients were excluded post-randomization (A1c <8%). Of 143 eligible patients, 137 encounters (65 in the usual care arm, 72 in QBSAFE) yielded evaluable videos. QBSAFE was used as intended in 61 (85%) QBSAFE arm encounters. Conversations about burden of treatment related to non-pharmacological interventions (17 vs 33, p= 0{middle dot}04) and taking medications (11 vs 33, p= 0{middle dot}0008) and about the patients challenging environment (2 vs 10, p= 0{middle dot}04) were more prevalent in the QBSAFE group. There was no difference in the rate of conversations about metabolic management or of new care plans as a result of conversations between groups. InterpretationWhile there was a difference in the types of conversations observed between the two study arms, this difference was small and only apparent in a few domains. Future work could aim to modify the QBSAFE cards to more effectively stimulate patient-centered discussions and to further prepare clinicians to respond to a variety of issues raised during the clinical visit. FundingThis work was supported by funding from the National Institute of Diabetes and Digestive and Kidney Diseases (R01DK129616).

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.

IntroductionPrevious studies have shown that Aquamin(R), a multi-mineral extract from red marine algae, enhances barrier integrity proteins in the human colon. These findings prompted further investigation into Aquamin(R)s effects on gastrointestinal barrier function and permeability. MethodsSubjects with mild or in remission ulcerative colitis (UC) and healthy controls were enrolled in an open-label trial and received Aquamin(R) capsules (800 mg calcium/day) for 90 days. Intestinal permeability was evaluated before and after the 90-day intervention by urinary mannitol excretion after ingestion of a 5 g mannitol solution, with collections across several time intervals (pre-drink, 0-2 h, 2-8 h, and 8-24 h). The primary outcome was the change in mannitol excretion. Serum samples were also collected to assess liver and renal function. ResultsIn this pilot study (NCT04855799), which included UC patients and healthy controls (n = 8 per group), baseline urine mannitol levels in the 0-2 h sample were 54% higher in UC patients compared to healthy subjects (p = 0.006). Following 90 days of Aquamin(R) supplementation, urinary mannitol levels in UC patients decreased by 28%, 26%, and 41% at the 0-2 h, 2-8 h, and 8-24 h timepoints, respectively; the reduction at the 0-2 h interval reached statistical significance (p = 0.015). Overall, Aquamin(R) supplementation reduced total post-intervention mannitol excretion by 29% (p = 0.024). Aquamin(R) was well tolerated, with no serious adverse events reported. The serum metabolic panel revealed a modest but statistically significant reduction in alkaline phosphatase levels after 90 days of intervention. ConclusionThese results provide preliminary evidence that Aquamin(R) supplementation beneficially modulates gut barrier function and supports epithelial integrity in UC patients. These findings support further investigation of Aquamin(R) as a safe and promising adjunct to current UC management strategies, with potential utility as a barrier therapy in UC. SummaryAquamin(R) supplementation for 90 days reduced intestinal permeability in ulcerative colitis patients, as measured by urinary mannitol excretion. The intervention was well tolerated, suggesting Aquamin(R) may be a safe, promising adjunct for enhancing gut barrier function in UC management.

Decentralized clinical trials offer a scalable approach to evaluate patient research in real-world settings. The COSMOS-DIGITAL study (NCT06761703) was designed to assess the feasibility of recruiting patients using antiobesity medications from an online patient community and aimed to evaluate participants willingness to consent to and complete fully decentralized surveys and at-home self-blood testing. Three-quarters (n = 151; 75.5%) of participants completed all self-collected capillary blood samples, Patient-Reported Outcomes in Obesity (PROS) surveys, and nausea-related surveys. Over 83% of participants completed the surveys (PROS: n = 167; 83.5%; daily nausea: n = 168; 84.0%), and 93% (n = 142/152) of collected blood samples were sufficient or partially sufficient for testing. Overall, participants were satisfied with the at-home blood collection device. Digitally enabled, fully decentralized studies can capture blood samples and survey responses as well as important aspects of patient treatment experiences, adding value to data collected in randomized controlled trials.

IntroductionBurnout among healthcare professionals remains a critical public health issue linked to impaired cognition, emotional exhaustion, and diminished clinical performance. Structured breathing practices have demonstrated promise in improving autonomic regulation and cerebral oxygenation, yet their feasibility and acceptability in real-world healthcare settings remain underexplored. ObjectivesThis single-arm pilot feasibility trial aims to evaluate the feasibility, acceptability, and implementation appropriateness of a structured breathing-based intervention for healthcare professionals across community-based Mayo Clinic Health System (MCHS) sites. Secondary objectives include assessing usability and engagement with the mobile breathing platform, while exploratory analyses will examine preliminary signals of change in psychological well-being and cerebral hemodynamics. Methods and AnalysisA total of 40 physicians and nurses reporting moderate or greater burnout will be enrolled across four MCHS sites. Participants will complete a four-month structured breathing program delivered primarily online, supported by a mobile application for practice tracking. Assessments will occur at baseline, 2 months, and 4 months, with optional functional near-infrared spectroscopy (fNIRS) measures of cerebral oxygenation collected at baseline and 4 months in a subset. Primary outcomes include (1) recruitment yield, retention, and adherence rates; (2) acceptability and participant satisfaction (survey and qualitative feedback); and (3) implementation appropriateness measured by the Acceptability of Intervention Measure (AIM), Intervention Appropriateness Measure (IAM), and Feasibility of Intervention Measure (FIM). Secondary outcomes assess digital engagement and usability through mobile analytics and the System Usability Scale (SUS). Exploratory outcomes evaluate psychological indicators--burnout, depression, anxiety, perceived stress, sleep, fatigue, professional fulfillment, and resilience--and physiological endpoints (fNIRS). Analyses will be descriptive, summarizing feasibility metrics with 95% confidence intervals. Progression criteria (recruitment [&ge;]75%, retention [&ge;]80%, adherence [&ge;]70%, AIM/IAM/FIM [&ge;]4.0) will determine readiness for a definitive hybrid effectiveness-implementation trial. Ethics and DisseminationThe study is approved by the Mayo Clinic Institutional Review Board (IRB # 25-009320). All participants will provide informed consent. Study procedures ensure confidentiality, cultural sensitivity, and participant safety. Data will be securely stored in REDCap and disseminated through peer-reviewed publications and scientific conference ClinicalTrials.gov IDThe study has been prospectively registered at ClinicalTrials.gov (Identifier NCT07218458). Strengths and LimitationsO_LIEvaluates a structured breathing-based intervention using both subjective and objective indicators of feasibility, including recruitment, retention, adherence, and implementation appropriateness. C_LIO_LIIntegrates mobile application analytics with standardized implementation measures (AIM, IAM, FIM) to capture digital engagement and real-world usability. C_LIO_LIIncorporates functional near-infrared spectroscopy (fNIRS) to explore physiological mechanisms underlying burnout recovery, linking cerebral oxygenation to behavioral outcomes. C_LIO_LIConducted across diverse community-based Mayo Clinic Health System sites, enhancing ecological validity and relevance to decentralized clinical settings. C_LIO_LILimitations include the single-arm, region-restricted design, modest sample size, and reliance on volunteer participants, which constrain generalizability and preclude causal inference; exploratory outcomes are intended to guide future trial refinement. C_LI

BackgroundBRASH syndrome, characterized by bradycardia, renal failure, atrioventricular nodal blockade, shock, and hyperkalemia, is a recently described clinical entity that remains underrecognized. Current evidence is limited to case reports and small case series, and the pharmacological patterns underlying this syndrome have not been systematically evaluated. MethodsWe conducted a retrospective pharmacovigilance study using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) from January 2004 to March 2025. Individual case safety reports explicitly coded as BRASH syndrome were identified and deduplicated. Associations between BRASH syndrome and individual drugs were assessed using Reporting Odds Ratios (RORs) and Information Components (ICs) with 95% confidence intervals. Drugs showing positive disproportionality signals were categorized according to their presumed role in the BRASH pathophysiological cascade. ResultsA total of 1,081 reports were included. The median age of patients was 74 years (interquartile range, 64-82); 45.5% were female, 38.7% were male, and sex was not reported in 15.8% of cases. All cases were classified as serious adverse drug reactions, including 7.1% fatal and 34.4% life-threatening events. Strong disproportionality signals were observed for atrioventricular nodal blocking agents, including metoprolol (ROR, 58.6; 95% CI, 52.0-66.1), verapamil (ROR, 52.5; 95% CI, 43.4-63.3), and carvedilol (ROR, 28.7; 95% CI, 24.4-33.6). Additional signals involved drugs plausibly contributing to renal dysfunction or hyperkalemia. Multiple pharmacologically relevant drugs were frequently reported within individual cases. ConclusionsBRASH syndrome is associated with combinations of cardiovascular and renal-active medications rather than single-drug exposure, supporting its interpretation as a polypharmacy-driven clinical syndrome in vulnerable patients.

ImportanceCurrent guidelines from the World Health Organization, Centers for Disease Control and Prevention, and Academy of Breastfeeding Medicine recommend discarding all milk remaining in bottles immediately after infant feeding. However, these recommendations lack supporting microbiological evidence from studies of actual infant feeding, imposing substantial financial and emotional burden on the 78 million families worldwide who bottle-feed their infants. ObjectiveTo determine (1) the financial, emotional, and time burden associated with bottle feeding and parental milk disposal practices, and (2) bacterial growth in leftover human milk and formula under different storage conditions. Design(1) Cross-sectional online survey (January 2023-February 2024) and (2) prospective microbiological cohort study. Setting(1) Online survey, (2) infants recruited in Hannover, Germany Participants(1) Survey respondents (n=1056; 99% mothers) and (2) healthy, full-term, bottle-fed infants (n=44; 17 humanmilk, 27 formula) aged 0-12 months. Main Outcomes and MeasuresParental burden scores, milk disposal frequency, and bacterial colony-forming units (CFU)/ml in milk samples before feeding, immediately after feeding, and at 4, 8, and 24 hours post-feeding at 4{degrees}C and 20{degrees}C. ResultsAmong surveyed parents, 46% discarded leftover milk daily, yet 84% reported they would keep milk longer if deemed safe. In microbiological testing, median bacterial burden in humanmilk increased from 4200 CFU/ml (range 300-350,000) pre-feeding to 24,600 CFU/ml (range 1900-29,004,400) post-feeding, but showed no significant further increase at 4 hours (p=0.82) or 8 hours (p=0.64) when stored at either 4{degrees}C or 20{degrees}C. Formula showed similar stability: median CFU/ml increased from 0 (range 0-10,700) to 11,700 (range 1900-630,000) post-feeding, with no significant change at 4 hours (p=0.91) or 8 hours (p=0.73) at either temperature. Significant bacterial growth occurred only after 24 hours at 20{degrees}C (p<0.001). Conclusions and RelevanceBacterial burden in leftover infant milk remained stable below concerning thresholds for 8 hours when refrigerated and 4-8 hours at room temperature, challenging current guidelines that mandate immediate disposal. Evidence-based guideline revision could reduce financial burden and milk waste for families around the globe without compromising infant safety. Key PointsO_ST_ABSQuestionC_ST_ABSHow long is it safe to offer leftover milk in a bottle to an infant that has previously drunk from it? FindingsThe number of bacteria in leftover human milk or formula did not significantly increase from 0 to 8h post-feeding in milk bottles sampled from 44 infants, regardless of whether the milk was kept at room temperature or refrigerated. MeaningLeftover milk may be safely reoffered beyond the limits of the current guidelines.

ObjectivePsychological distress in cancer is associated with poorer quality of life, poorer treatment adherence and outcomes, and higher healthcare costs. The current study aimed to provide evidence on the effectiveness of the Progressive Muscle Relaxation program in female patients with breast cancer at Goa Medical College, Goa, a state in the Western part of India. This study will help to explore the level of anxiety, depression, and fatigue and provide suitable recommendations to reduce anxiety, depression, and fatigue among cancer patients. MethodsIt was a Randomised Controlled Trial. The study was conducted in Surgery Wards 106 and 109 at Goa Medical College. Adult women [&ge;] 18 years of age with a new diagnosis of breast cancer who have undergone surgery as their primary mode of treatment are included in the study. Sixty patients were randomly divided into two groups of 30 each, using a block randomization method with ten numbered sealed opaque envelopes. Fifty-eight people completed the study. The intervention entailed a 20-minute Progressive Muscle Relaxation (PMR) session, which started with Deep Breathing and Guided Imagery (GI) sessions given to one group. Both groups were evaluated for anxiety, depression, and fatigue levels using the Zung Anxiety Scale, Beck Depression Inventory, and Fatigue Scale at baseline and after the two-week intervention. ResultsFifty-eight people completed the study. The participants in both groups had similar sociodemographic characteristics and clinical profiles. After two weeks of intervention, the intervention group showed significant reductions in anxiety (51.71 {+/-} 2.89 to 38.52 {+/-} 6.32, p [&le;] 0.001), depression (11.48 {+/-} 2.93 to 6.16 {+/-} 2.98, p [&le;] 0.001), and fatigue (23.29 {+/-} 4.12 to 16.88 {+/-} 4.73, p [&le;] 0.001). ConclusionsThis study highlights the effectiveness of Progressive Muscle Relaxation (PMR) and Guided Imagery (GI) in reducing anxiety, depression, and fatigue in breast cancer patients. These nonpharmacological techniques serve as valuable complementary therapies, helping manage emotional distress and prevent symptom progression during treatment. Trial registration number and dateCTRI (Clinical Trial Registry of India) Registration was done in February 2021 from the Clinical Trial Registry of India, with Reg. number CTRI/2021/02/030996.