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Stigma, discrimination-related events, and determinants among adult people living with systemic lupus erythematosus (SLE): Systematic review and indicator-level meta-analysis.

BackgroundSystemic lupus erythematosus (SLE) is a complex autoimmune disease with 0.4 million new cases diagnosed annually. With its wide variety of visible and invisible manifestations, people living with SLE report being exposed to stigmatization, which impacts their personal and professional lives. However, the current literature is unclear on whether healthcare management teams assess this concern during follow-up. This study aims to synthesize existing evidence on the prevalence and determinants of stigma among people living with SLE.MethodsThis systematic review and meta-analysis gathered evidence from observational studies identified from three databases on 16 July 2025. Dual independent screening, data extraction, and risk-of-bias assessment (using the Newcastle-Ottawa Scale) were performed. Results were synthesized using descriptive statistics, narrative synthesis, and indicator-level meta-analyses.ResultsWithin the past two decades, 11 studies comprising 2254 people living with SLE reported and measured stigma- and discrimination-related events using various scales. Stigma was found to be prevalent across its three constructs: interpersonal, perceived, and intrapersonal stigma. This review demonstrated that people living with SLE reported a moderate overall burden of stigma (34.71 [95% CI 26.15, 43.27]), with average stigma scores indicating psychological impact. Additionally, nearly one in two persons (46% [95% CI 28-66%]) experienced at least one form of stigma or discrimination, most commonly social isolation and unfair treatment. Mental health associations were correlated with higher stigma burden.ConclusionThis review demonstrates that stigma and discrimination are not just social challenges but also critical determinants of health. With cautious interpretation, pooled evidence reveals a consistent high prevalence of stigma and discrimination, which act as "toxic" stressors, creating a vicious cycle with psychological stress and psychiatric manifestations and disease activity. There is an urgent clinical need to move beyond a mere biological approach to disease assessment and management and to begin screening for the "invisible" burden of invalidation and discrimination.

Humans

Reducing state anxiety with alpha-frequency transcranial alternating current stimulation.

BACKGROUND: Anxiety reactivity to acute stress is a transdiagnostic vulnerability factor. We tested whether a single session of alpha-frequency transcranial alternating current stimulation (tACS) targeting the frontoparietal control network reduces stress-evoked state anxiety in healthy adults. METHODS: In a randomized, blinded, sham-controlled study, 42 participants (mean age 58.9 years) completed an acute stress task before and after stimulation. The task was an adapted moving-circles paradigm in which circle collisions triggered a brief aversive event (mild electric shock plus unpleasant noise and a white flash). Active stimulation consisted of 20 min of 10-Hz tACS (2.0 mA/channel; 30-s ramp up/down) delivered via electrodes at F3, P3, Cz, and T7 (0° phase at F3/P3; 180° at Cz/T7). Sham stimulation used the same montage and ramp periods but no sustained current. RESULTS: State anxiety showed a significant Time × Protocol interaction (F(1,35) = 4.22, p = .047): STAI-S decreased after active tACS (Δ = -3.16) but increased slightly after sham (Δ = +1.17). Perceived stress appraisal (SAAS) did not change. Resting-state alpha power at F3/P3 showed no reliable pre-post effects. During the task, left-frontal relative alpha differed by protocol and showed a trend toward larger increases following active tACS. Electrodermal and pupil indices changed across sessions in both groups, with no differential stimulation effects. CONCLUSIONS: A single alpha-tACS session produced a modest, selective reduction in stress-evoked state anxiety, supporting oscillatory neuromodulation as a scalable approach to dampen anxiety reactivity.

Humans

Exercise with motor cortex high-definition transcranial direct current stimulation enhances cardiovascular efficiency and lower-limb function in multiple sclerosis: A crossover, double-blind, and proof-of-principle study.

Combining exercise with high-definition transcranial direct current stimulation (HD-tDCS) could offer a strategy to help people with Multiple Sclerosis improve outcomes. In this crossover study, participants with MS (Expanded Disability Status Scale &#x2265;3.0, n&#x202f;=&#x202f;12) and controls (n&#x202f;=&#x202f;10) completed baseline testing, followed by three randomized experimental conditions: 1) exercise+active HD-tDCS; 2) exercise+sham HD-tDCS; and 3) HD-tDCS alone. Exercise performance metrics [heart rate, work rate, heart rate-to-work rate (HR/WR) ratio, and perceived exertion] were compared across the exercise conditions. Secondary outcomes included the Symbol Digit Modalities Test (SDMT), Timed 25-Foot Walk (T25F), Nine-Hole Peg Test (9HPT), and acute symptom ratings (fatigue and pain), assessed pre-, immediately post-, and 1h-Post. Cardiovascular efficiency (HR/WR ratio) significantly improved during exercise+HD-tDCS compared to exercise alone, particularly in older MS participants (p&#x202f;=&#x202f;0.010). SDMT declined immediately post HD-tDCS alone, 1h-post-exercise alone, and at both time points during exercise+active HD-tDCS (p&#x202f;<&#x202f;0.05). Both groups increased walking speed only post-exercise+active HD-tDCS, while no condition affected upper-limb function (p&#x202f;<&#x202f;0.05). These results are in line with the tDCS literature in the general population, suggesting that tDCS improves exercise performance and selectively improves engaged motor function. The trade-off between physical and cognitive outcomes underscores the importance of personalized neuromodulation strategies in neurorehabilitation to maximize therapeutic benefits while minimizing adverse effects, and warrants further large-scale, long-term investigations of this approach in MS.

Humans

Protocol for project FIERCE: A randomized controlled trial to evaluate a positive emotion-focused meditation intervention for physicians with elevated stress.

INTRODUCTION: Nearly 80% of healthcare providers experience adverse psychological symptoms (e.g., depression, burnout, sleep disturbance) stemming from workplace stressors. Elevated levels of stress have been associated with unfavorable occupational, patient, and provider-related outcomes, imposing a heavy burden on a strained system. Given the impact of stress on both employee and patient health, effective interventions are urgently needed to reduce distress and promote well-being among healthcare professionals. Mindfulness-based interventions show promise for addressing these challenges. We developed a six-week, remotely delivered mindfulness intervention, the Building Emotional Strength Training (BEST) program, based on the Buddhist Four Immeasurables practice to cultivate the distinct emotional qualities of loving-kindness, compassion, joy, and equanimity. The present study aims to evaluate the feasibility and efficacy of a Four Immeasurables-based mindfulness intervention on perceived stress (primary outcome), burnout, depressive symptoms, and inflammatory biomarkers, while enhancing psychological well-being and sleep quality (secondary outcomes) in physicians. We will also investigate potential mediators of intervention effects, including compassion, positive affect, equanimity, and mindfulness. METHOD: We will enroll 90 full-time physicians in a remote, two-arm randomized controlled trial with 1:1 allocation to either the meditation intervention or waitlist control. Participants will complete self-report questionnaires and provide blood samples at baseline, mid-course, and post-intervention to assess outcomes and mediators. DISCUSSION: The project aims to advance the study of mindfulness-based interventions that reduce distress and promote well-being through practices that cultivate prosocial and altruistic feelings toward oneself and others. While mindfulness interventions have gained considerable interest, none have specifically drawn from the Four Immeasurables practice to target loving-kindness, compassion, joy, and equanimity. This novel investigation could expand our understanding of practices that foster kindness and compassion to reduce distress in an at-risk population. TRIAL REGISTRATION: ClinicalTrials.gov NCT07283744, registered on 2025/10/14. The Open Science Framework, registered on 2026/06/26.

Humans

Use of wearable technologies for physical activity promotion in older adults: A systematic review.

This systematic review, conducted according to PRISMA guidelines and registered in PROSPERO (CRD420251055299), examined the use of wearable technologies for promoting physical activity (PA) in adults aged 60 years and older. Searches across five databases (PubMed, Scopus, Web of Science, CINAHL, Cochrane) identified 2438 records, of which only six randomized controlled trials published between 2021 and 2025 met inclusion criteria, with sample sizes ranging from 36 to 551 participants and mean ages between 65 and 79 years. Given the small number of included studies, findings should be interpreted as preliminary. The studies ranged from the standalone use of commercial trackers (Fitbit, Polar, ActiGraph) to multicomponent interventions combining wearables with physiotherapist feedback, telephone counseling, web-based platforms, or interactive cognitive-motor training. Wearables used alone, as in the REACT trial, produced small or non-significant PA effects. In contrast, interventions integrating devices with personalized feedback, professional support, or digital platforms, such as PROMOTE and TASMANIA, were associated with more consistent improvements in PA, physical function, and cognitive outcomes. Multicomponent programs, such as PEER and ICMT, reported broader benefits, including cognition, balance, and reductions in sedentary behavior, though these findings derive from individual trials and require replication. Risk of bias, assessed with the Cochrane Risk of Bias tool version 2 (RoB 2.0), was rated as "some concerns" for five studies and low for only one, mainly due to gaps in randomization reporting, missing data, and lack of preregistration. Tentatively, and based on a very limited evidence base, wearables may have greater impact when embedded within broader behavioral systems, incorporating feedback, coaching, or interactive components, rather than when used in isolation as passive monitoring tools. Adherence and psychosocial outcomes appeared related to comfort and perceived usefulness among older adults, though larger and more robust trials are needed to confirm these patterns.

Humans

Barriers to physical activity in patients with systemic lupus erythematosus in the UK.

INTRODUCTION: Physical activity (PA) may play an important role as a non-pharmacological addition to the management of SLE for disease control and reduction of cardiovascular risk factors. Those with SLE have been reported to engage in PA less than the general population. OBJECTIVE: To describe PA patterns and patient-reported barriers to PA for people with SLE in the UK. METHODS: An online survey was conducted of adults aged&#x2009;&#x2265;&#x2009;18 years. Participants were recruited from posters in outpatient clinics, newsletters and Lupus UK social media platforms. Survey questions included demographic information, perception of disease activity, the International Physical Activity Questionnaire (IPAQ) and specific leisure time questions. RESULTS: Two hundred sixty-eight patients participated, with a median (IQR) age of 51 (39-59) years and SLE disease duration of 10 (4-20) years&#xa0;were included. SLE-diagnosis was collected by self-report. In those with complete IPAQ data, 178/228 (79.1%) were in a moderate/high activity group. Participants in this group were more likely to be in employment and had lower levels of fatigue and pain. Fatigue was the most reported barrier to PA, irrespective of activity levels. Participants in the low PA group were more likely to have SLE-specific barriers such as higher disease activity and higher pain scores. CONCLUSIONS: Perceptions and preferences in relation to PA differ greatly between individuals with SLE. The most common self-reported barrier to PA was fatigue. Exploration of individual perceptions of PA should form part of consultations, to address perceived barriers. Key Points &#x2022; Some patients with self-reported SLE can meet WHO physical activity targets, especially those who remain in work. &#x2022; Fatigue is the most frequently reported barrier to physical activity for patients, irrespective of their activity levels. &#x2022; People are less likely to engage in PA if they believe it will negatively affect their SLE.

Humans

Virtual reality physical education and adolescents' exercise interest and physical fitness: An explanatory sequential mixed-methods randomized trial with exploratory pathway analysis.

Traditional physical education (PE) faces declining student interest and limited fitness gains. Virtual reality (VR) offers immersive, gamified experiences, but evidence regarding its effectiveness and explanatory pathways remains limited. This explanatory sequential mixed-methods randomized trial assigned 360 adolescents (aged 13-16) from three middle schools to either VR-supported PE (n&#xa0;=&#xa0;180) or conventional PE (n&#xa0;=&#xa0;180) for 12&#xa0;weeks, with a 4-week follow-up. Outcomes included exercise interest (validated scale), physical fitness (coordination via MABC-2, cardiorespiratory endurance via the 20-m shuttle run, explosive power via the standing long jump, and speed via the 10-m sprint), and accelerometer-measured physical activity. The qualitative component involved 38 unique students: 32 completed individual semi-structured interviews, and six additional students participated only in focus groups. Three-level linear mixed-effects models and exploratory structural equation modeling were used. The VR group showed significantly greater improvements in exercise interest (d&#xa0;=&#xa0;0.78), coordination (d&#xa0;=&#xa0;0.62), cardiorespiratory endurance (d&#xa0;=&#xa0;0.55), and speed (d&#xa0;=&#xa0;0.48) than the control group (all p&#xa0;<&#xa0;0.001), but not in explosive power (d&#xa0;=&#xa0;0.12, p&#xa0;=&#xa0;0.148). Effects were partially retained at follow-up (interest d&#xa0;=&#xa0;0.65, coordination d&#xa0;=&#xa0;0.48, endurance d&#xa0;=&#xa0;0.42, and speed d&#xa0;=&#xa0;0.30), a pattern not fully consistent with a purely novelty-driven explanation. Exploratory mediation identified exercise interest as a statistically compatible explanatory pathway (indirect effect&#xa0;=&#xa0;0.34, 95% CI [0.22, 0.46]), although the timing of measurement precludes causal interpretation. Qualitative findings contextualized these results by highlighting immersion, feedback, self-efficacy, and perceived transfer. VR-supported PE may enhance adolescents' exercise interest and selected fitness dimensions, but its limited effect on explosive power and possible novelty contribution indicate that it should complement, rather than replace, conventional PE. Longer-term studies are needed.

Humans

Social support and cognitive function in postmenopausal women.

OBJECTIVE: An active social lifestyle may protect against cognitive decline in older adults, but few studies have examined specific social support dimensions in relation to specific cognitive domains. This study examines associations between social support dimensions and cognitive function in older women. METHODS: The Early versus Late Intervention Trial with Estradiol (ELITE) was a randomized, double-blinded, placebo-controlled trial of oral 17&#x3b2;-estradiol versus placebo in postmenopausal women, designed primarily to evaluate the timing hypothesis on atherosclerosis progression and cognitive decline; the present analysis is a secondary, hypothesis-generating examination of the psychosocial substudy data (2009-2012). A total of 448 women completed psychosocial assessments every 6 months. Cognitive function was assessed at baseline, 2.5, and 5 years using composite scores for executive function, verbal memory, visual memory, and global cognition derived from 14 standardized tests. Perceived social support was assessed using the Medical Outcomes Study-Social Support Survey (MOS-SSS; 0-100 scale). Paired cognitive-psychosocial assessments were analyzed using linear mixed-effects models adjusted for age, marital status, blood pressure medication, BMI, education, income, race, and randomized treatment (hormone therapy or placebo). RESULTS: A total of 298 women (mean age 60.3&#xa0;y) provided 322 paired visits. Positive associations were observed between instrumental social support and visual memory (&#x3b2;(SE)=0.0044(0.0022), 95% CI: -0.00002 to 0.0088, P=0.051) and between positive social interaction and global cognition (&#x3b2;(SE)=0.0092(0.0046), 95% CI: 0.0001-0.0182, P=0.047). In age-stratified analyses, the positive social interaction-global cognition association was significant among women <65 years (P=0.042) but not women &#x2265;65 years (P=0.34). No association survived false discovery rate (FDR) correction for multiple comparisons. CONCLUSIONS: In this sample of healthy middle- to older-aged women, no association between specific dimensions of social support and cognitive domains was statistically significant after correction for multiple comparisons. These hypothesis-generating findings suggest any association is modest at best and warrant confirmation in studies designed specifically for this question.

Cognitive function

Contrast Heat-Cold Versus Thermoneutral Showering in Trained Combat Sport Athletes: A Randomized Field Trial of Recovery Outcomes.

Contrast heat-cold showering is popular for recovery, but multisystem evidence and persistence after cessation remain unclear. To evaluate whether a 4-week post-training contrast heat-cold shower intervention produces an integrated recovery profile across four domains (autonomic, endocrine, perceptual, and microvascular) rather than testing a single isolated physiological pathway, across baseline (T0), post-intervention (T1), and 2-week wash-out (T2). Sixty combat-sport athletes were randomized to contrast showers (10 min alternating warm 38-40&#xb0;C and cold 13-15&#xb0;C) or an active thermoneutral-shower comparator (10 min, 32-34&#xb0;C) after training for 4 weeks. Primary analyses were per-protocol (&#x2265; 75% compliance; n = 57), with intention-to-treat sensitivity analyses. Outcomes were Total Quality Recovery (TQR), morning salivary cortisol (two mornings averaged), resting HRV, and post-occlusive reactive hyperemia (PORH). From T0 to T1, favorable between-group changes were observed for resting HR (&#x394;&#x394; -2.10 bpm, 95% CI -2.24 to -1.96; g -0.65; p < 0.001), lnRMSSD (&#x394;&#x394; 0.123 log units, 95% CI 0.108 to 0.137; g 0.74; p < 0.001), with similar T1 effects for RMSSD and SDNN, and TQR (&#x394;&#x394; 0.61 points, 95% CI 0.27 to 0.95; g 0.80; p < 0.001). These T1 autonomic and perceptual changes were not maintained at T2 (all T2-T0 &#x394;&#x394; p > 0.05). Cortisol and PORH-derived outcomes showed no statistically clear between-group differences at T1 or T2 (all p > 0.05). Compared with thermoneutral showering, 4 weeks of post-training contrast heat-cold showering produced short-term favorable between-group changes in autonomic regulation and perceived recovery, but not in morning cortisol or PORH-derived microvascular reactivity. These effects were not maintained after wash-out; therefore, causal attribution to the shower intervention alone and claims of persistent physiological adaptation should be made cautiously. Trial registration: ISRCTN15418049.

Humans

Visualizing the future: impact of holographic visualization on teaching minimally invasive veneer preparation: a randomized controlled trial.

BACKGROUND: Minimally invasive veneer preparation in prosthodontic education requires advanced spatial understanding and psychomotor precision. Although immersive technologies are increasingly used in dental education, evidence regarding the educational effectiveness of holographic visualization in prosthodontics remains limited. This randomized controlled trial evaluated the impact of holographic visualization on preparation quality and student-reported educational outcomes during preclinical training in minimally invasive veneer preparation. METHODS: Sixty undergraduate dental students were randomly assigned to receive either conventional two-dimensional photographic visualization (n&#x2009;=&#x2009;30) or holographic three-dimensional visualization (n&#x2009;=&#x2009;30). Following a standardized calibration session and baseline preparation, participants performed a second veneer preparation after exposure to the assigned visualization modality. Preparations were independently assessed by two blinded evaluators using a predefined scoring rubric. Within-group changes were analysed using Wilcoxon signed-rank tests, and between-group differences were assessed using analysis of covariance adjusted for baseline performance. Student-reported outcomes were compared using Mann-Whitney U tests with false discovery rate correction. RESULTS: Both groups showed significant improvements in preparation quality from baseline to post-intervention (both p&#x2009;<&#x2009;0.001). However, no significant between-group differences were observed (adjusted mean difference: 0.60 points; 95% confidence interval: -0.48 to 1.67; p&#x2009;=&#x2009;0.269). Overall student-reported outcomes were comparable between groups. Spatial understanding showed the largest between-group effect in favour of holographic visualization, although this difference was not significant after correction for multiple comparisons. Holographic visualization was highly accepted by students, and 70% supported its future integration into dental education. CONCLUSIONS: Although holographic visualization did not significantly improve immediate preparation quality compared with conventional two-dimensional photographs, it was highly accepted by students and showed the largest observed effect for perceived spatial understanding. These findings suggest that holographic visualization may primarily support spatial understanding and represent a valuable adjunct for teaching complex three-dimensional concepts in preclinical prosthodontic education. TRIAL REGISTRATION: German Clinical Trials Register (DRKS), DRKS00040713, prospectively registered on 22 June 2026.

Humans

Effects of essential amino acid supplementation on musculotendinous recovery following eccentric plantar flexor exercise: a randomized controlled trial.

BACKGROUND: Exercise-induced muscle damage (EIMD) resulting from eccentric contractions leads to transient impairments in muscle function. Essential amino acids (EAAs) stimulate muscle protein synthesis and may support recovery following damaging exercise. However, limited research has examined the effects of EAAs on muscle function following eccentric plantar flexor exercise. The purpose of this study was to examine the effects of EAA supplementation on indirect markers of muscle and musculotendinous recovery following EIMD. METHODS: Thirty-six recreationally active males (age: 21.2&#x2009;&#xb1;&#x2009;2.7&#x2009;years) were randomly assigned to an EAA group (10&#x2009;g of EAAs), placebo (10&#x2009;g of maltodextrin), or control (no supplementation). Supplements were consumed 30&#x2009;minutes before and immediately after an eccentric plantar flexor protocol (4&#x2009;&#xd7;&#x2009;50 repetitions followed by one set to failure) and during the 72&#x2009;hours recovery period. Indirect markers of muscle damage were assessed pre-exercise, immediately post-exercise, and 24, 48, and 72&#x2009;hours post-exercise, consisting of perceived soreness (NPRS), pain pressure threshold (PPT), calf muscle thickness and Achilles tendon thickness (ultrasound), and calf circumference. RESULTS: The eccentric protocol elicited responses consistent with EIMD, including increased soreness (p&#x2009;<&#x2009;0.001), increased calf muscle thickness and circumference (p&#x2009;<&#x2009;0.001), and reduced PPT (p&#x2009;=&#x2009;0.018). EAA supplementation attenuated soreness at 24&#x2009;hours compared with placebo. Calf muscle thickness increased following exercise in both groups; however, swelling returned to baseline by 72&#x2009;hours in the EAA group but remained elevated in placebo (Condition&#x2009;&#xd7;&#x2009;Time, p&#x2009;<&#x2009;0.001). Achilles tendon thickness decreased immediately post-exercise (p&#x2009;=&#x2009;0.005) but was not influenced by supplementation. CONCLUSIONS: EAA supplementation modestly reduced soreness and was associated with faster recovery of muscle swelling but did not influence tendon morphology within 72&#x2009;hours.

Humans

Comfort and Usability of Digital Versus Conventional Custom-Fit Mouthguards: A Randomized Clinical Trial.

BACKGROUND/OBJECTIVES: The use of mouthguards protects teeth and the supporting tissues against impacts. Digital impressions and 3D-printed models can reduce manufacturing steps and minimize discomfort. This study evaluated the fit, comfort, and usability of custom-made mouthguards, obtained by conventional and digital workflow, in amateur athletes. MATERIALS AND METHODS: Amateur athletes were recruited for this randomized, double-blind, crossover clinical study. Each participant received two 4-mm-thick custom-fit mouthguards made of ethylene vinyl acetate (EVA) sheets using two protocols: conventional impression using alginate to produce dental stone cast (CMP) and intraoral digital scanning to produce 3D-printed resin models (DMP). Each mouthguard was worn during all training and matches over 3&#x2009;months. The order of mouthguard use was randomly assigned. Patient satisfaction with the impression protocol and mouthguard use, model accuracy, and mouthguard fit were assessed. RESULTS: Overall, 46 participants completed the study. The DMP protocol required less execution time (p&#x2009;=&#x2009;0.023), caused less discomfort (p&#x2009;=&#x2009;0.018), anxiety (p&#x2009;=&#x2009;0.008), nausea (p&#x2009;=&#x2009;0.027), difficulty breathing (p&#x2009;<&#x2009;0.001), and unpleasant taste (p&#x2009;=&#x2009;0.006) compared to the CMP protocol. The pain (p&#x2009;=&#x2009;0.971) perceived by the participants was similar in both impression protocols. The CMP-mouthguards were considered to be better fitting by the majority of participants (p&#x2009;=&#x2009;0.027). Between-group comparisons revealed that DMP-mouthguard caused less discomfort immediately postadaptation (p&#x2009;=&#x2009;0.034), with no significant differences observed at 30 or 90&#x2009;days. CONCLUSIONS: The digital workflow demonstrated to be efficient in the fabrication of mouthguards. Digital impression was more comfortable, requiring less execution time, with more accurate printed models and produced mouthguards with reported comfort and fit levels similar to those manufactured conventionally.

Humans

Psychological impacts of APOE genotype disclosure among Latinos in New York City: a randomized controlled trial.

INTRODUCTION: Latinos face increased Alzheimer's disease (AD) risk but are underrepresented in studies of APOE genotype disclosure. We evaluated the psychological impacts of APOE disclosure in the Informaci&#xf3;n de la Enfermedad de Alzheimer para Latinos (IDEAL) study, a randomized controlled trial among Latinos in New York City. METHODS: Latino northern Manhattan residents without self-reported AD (mean age 52, 69% women, 49% college graduates) were randomized in the period August 2021 to July 2024 to receive AD risk estimates to age 85 incorporating APOE genotype, family history, and ethnicity (disclosure) or the same factors excluding APOE (non-disclosure). Bilingual genetic counselors delivered risk estimates to both groups, unmasked to randomization. Follow-up surveys were completed 6&#xa0;weeks, 9 months, and 15 months after risk delivery. Primary outcomes were impact of genetic testing in AD (IGT-AD) and Impact of Event Scale-Revised (IES-R). Secondary outcomes were changes from baseline in depression, anxiety, and perceived AD threat. Analyses used intention-to-treat with multiple imputation. RESULTS: Disclosure (N&#xa0;=&#xa0;194) and non-disclosure (N&#xa0;=&#xa0;180) groups did not differ on IGT-AD (mean disclosure-non-disclosure difference [MD] at 6 weeks: -1.5, p&#xa0;=&#xa0;0.14; 9 months: -1.2, p&#xa0;=&#xa0;0.35; 15 months: -2.0, p&#xa0;=&#xa0;0.07), IES-R (MD at 6 weeks: 0.00, p&#xa0;=&#xa0;0.98; 9 months: 0.01, p&#xa0;=&#xa0;0.84; 15 months: 0.03, p&#xa0;=&#xa0;0.64), or change in secondary outcomes. Occurrence of disclosure-related adverse events was similar in the disclosure (N&#xa0;=&#xa0;2) and non-disclosure (N&#xa0;=&#xa0;3) groups. DISCUSSION: In this Latino cohort, APOE disclosure did not have clinically significant adverse psychological effects, addressing an important evidence gap. TRIAL REGISTRATION: ClinicalTrials.gov NCT04471779.

Aged

Exploring the perceptions, experiences, and behaviours that nurses and midwives face in relation to sleep: A systematic review of qualitative evidence.

BACKGROUND: The importance of sleep for nurses and midwives is increasingly being recognised. Poor sleep is known to have negative impacts on physical health, mental wellbeing, and work performance. This has prompted efforts to promote and support staff sleep. However, further efforts are needed to understand how nurses and midwives consider and manage sleep to ensure that meaningful and effective interventions are adopted and sustained. AIMS: This review of qualitative evidence aims to examine nurses' and midwives' perceptions, experiences, and behaviours around sleep. METHODS: This review followed JBI's systematic meta-aggregative approach including development of an a priori protocol. A systematic search of six electronic databases (MEDLINE, Embase, Emcare, PsycINFO, CINAHL, and Scopus) was undertaken to identify qualitative studies that examine nurses' and midwives' perceptions, experiences, and behaviours related to sleep. The search was conducted on the 10th of October 2024. Study selection, quality appraisal, data extraction, and synthesis followed JBI approaches and the ConQual approach was used to report assessment of synthesised findings. RESULTS: Thirty-three studies were included for review, and 245 findings were aggregated into 24 categories and nine synthesised findings related to the perceptions, behaviours, and experiences. While sleep was perceived as important, poor sleep was often understood as an expected and inevitable part of the job and that there was a need to always be awake to provide continual care. Experiences influencing sleep related to personal circumstances and work-related factors, as well as professional training and institutional practices. A range of behaviours, including planning time to sleep, using sleep aids, modifying the sleep environment, and altering daytime behaviours were also described. CONCLUSION: This review identified a range of perceptions, behaviours, and experiences that may influence the sleep of nurses and midwives which are vital to supporting individual and workforce wellbeing and safe, effective clinical practice. Insights from this review can be used to better understand nurses' and midwives' relationship with sleep and to develop and enhance targeted sleep interventions and programs that aim to promote and support healthy sleep among nurses and midwives. Open Science Framework Registration: 10.17605/OSF.IO/F32UM.

Humans

Ketamine Plus Midazolam versus Fentanyl Plus Midazolam for Sedation and Analgesia during Image-guided Procedures in Interventional Radiology: Randomized Clinical Trial.

Background Opioid-benzodiazepine regimens remain common for radiologist-administered procedural sedation despite respiratory and analgesic effectiveness concerns. Purpose To compare intraprocedural pain and patient-reported experience between ketamine/midazolam and fentanyl/midazolam during image-guided procedural sedation. Materials and Methods This randomized clinical trial was conducted at a single academic center between June 2025 and February 2026. Adults undergoing image-guided lung or bone biopsy or abscess drainage were randomized to fentanyl/midazolam or ketamine/midazolam administered by interventional radiologists. Procedures were performed using US, CT, CT fluoroscopy, or combined CT and US guidance. The primary outcome was maximum intraprocedural pain (0-10 on the Numeric Rating Scale). Secondary outcomes included sedation depth, physiologic parameters, oxygen desaturation, patient-reported experience assessed using a modified Heidelberg questionnaire, and complications. Results Among 264 randomized procedures (132 procedures per group) in 260 participants (median age, 68 years [IQR, 61-75 years]; 135 [52%] female), ketamine/midazolam resulted in lower maximum intraprocedural pain than fentanyl/midazolam (mean difference, -1.4 points [95% CI: -2.0, -0.8]; P < .001). Pain scores greater than 4 occurred less frequently with ketamine/midazolam (2.3% vs 17%; absolute difference, 14 percentage points [95% CI: 8, 21]; P < .001). Ketamine/midazolam was associated with higher nadir oxygen saturation (mean difference, +1.4% [95% CI: 0.6, 2.2]; P = .001) and fewer oxygen desaturation events below 90% (three [2.3%] vs 13 [9.8%]; absolute difference, 7.6 percentage points [95% CI: 1.9, 13.3]; P = .02). Ketamine/midazolam produced deeper sedation and higher intraprocedural systolic blood pressure. Hallucinations occurred more frequently with ketamine/midazolam (15 [11.4%] vs five [3.8%]; absolute difference, 7.6 percentage points [95% CI: 1.3, 13.9]; P = .03), though overall procedural comfort, reduced recall, and perceived adequacy of sedation were improved. Procedure-related and sedation-related complications did not differ between groups. Conclusion Radiologist-administered ketamine/midazolam during image-guided procedural sedation improved analgesia and patient-reported experience with fewer hypoxemic events and no increase in complications compared with fentanyl/midazolam. Clinical trial registration no. NCT07040163

Aged

Addressing lignin composition and content via Arabidopsis arogenate dehydratase knockout and over-expression genotypes.

Following the down-selection of 14 Arabidopsis thaliana arogenate dehydratase (ADT) knockout and over-expression (OE) genotypes, the most highly contrasting quadruple knockout adt3/4/5/6 and ADT OE genotypes were subjected to proteomics, metabolomics, and scanning electron microscopy (SEM) analyses as needed, with results compared to Columbia wild-type (WT). The basal adt3/4/5/6 stem cross-sections, &#x223c;70% lignin content reduced, exhibited buckled vessel cell walls and partially detached xylary fibers, in contrast to WT and ADT4m/5&#x202f;m OE genotypes that did not. Anatomical defects primarily resulted from guaiacyl lignin level reductions in vessels with concomitant increased stem syringyl:guaiacyl (S/G) ratios. Phenylpropanoid and various upstream shikimate-chorismate pathway enzyme abundances, as well as specific monolignol oxidases (laccases/peroxidases), generally increased in adt3/4/5/6&#x202f;at different stem and rosette leaf growth/development stages, relative to WT. Opposite effects were largely observed with the ADT5m OE genotype. By contrast, flavonoid and glucosinolate pathway enzyme amounts varied. Such enzyme abundance increases were overall unproductive as adt3/4/5/6 was unable to restore WT, ADT4 OE, ADT5 OE, ADT5m OE, and ADT4m/5&#x202f;m OE secondary metabolite (lignin, phenylpropanoid, lignan, flavonoid, phenolic acid, and glucosinolate) levels. Conversely, ADT OE genotypes did not significantly increase programmed lignin levels or alter S/G compositions. In sum, proteomics analyses of adt3/4/5/6 and adt5 'perceived' that lignin and low molecular weight secondary metabolite amounts were not at 'programmed' levels as for WT and ADT OE genotypes but observed increases in relevant pathway protein abundances were futile. Notably though, proteomics analyses did not lead to predicting that lignin and associated biochemical pathways would have reduced metabolite levels, relative to WT and ADT OE genotypes. Genotype adt3/4/5/6, possibly the highest lignin level reduced genotype reported, did not utilize other phenolics to compensate. By contrast, the differential temporal and spatial deposition of cell wall oxidases again indicate the exquisite control over lignin deposition, and our lack of knowledge of precise lignin structure and assembly in subcellular regions of the lignified cell walls.

Lignin

Exercise Snacks Are Feasible to Perform in the Real World and Improve Physical Capacity for Adults Living With Non-Insulin Treated Type 2 Diabetes: A Randomised Trial.

AIMS: To investigate the feasibility and preliminary efficacy of a 12-week remotely-delivered exercise snacks (ES) intervention in adults with type 2 diabetes. MATERIAL AND METHODS: Insufficiently active adults with type 2 diabetes (N&#x2009;=&#x2009;69; 46 females; mean age&#x2009;&#xb1;&#x2009;SD: 58&#x2009;&#xb1;&#x2009;11&#x2009;years) were randomised to an ES or mobility/stretching comparator group (CON), which involved 4&#x2009;&#xd7;&#x2009;1-min bouts of either vigorous or low intensity exercise, respectively, on &#x2265;&#x2009;5&#x2009;days/week. The primary outcome was feasibility based on adherence. Secondary outcomes included exercise enjoyment (1-7 scale), rating of perceived exertion (RPE; 0-10 scale), heart rate (HR), haemoglobin A1c (HbA1c), blood biomarkers of cardiometabolic health, 30-s sit-to-stand capacity, grip strength, estimated maximal oxygen uptake, and anthropometrics. RESULTS: Weekly adherence (estimated marginal mean [95% confidence interval]: 18 bouts [16-21] for both groups; p&#x2009;=&#x2009;0.99) and total enjoyment (ES: 4.5 [4.1-4.8] vs. CON: 4.3 [4.0-4.7]; p&#x2009;=&#x2009;0.64) were high and not different between groups. Despite higher RPE (5.7 [5.4-6.1]) and peak HR (73 [70-77] % of age-predicted HR maximum) in ES versus CON (2.0 [1.7-2.4] and 61 [58-64] % of age-predicted HR maximum, respectively) (all p&#x2009;<&#x2009;0.001), there were no between-group differences in the change in any secondary outcome (all p&#x2009;>&#x2009;0.05) except for greater sit-to-stand capacity in ES after training (between-group effect estimate [95% confidence interval]: 1.9 repetitions [0.3-3.4]; p&#x2009;=&#x2009;0.02). CONCLUSIONS: Exercise snacks were feasible to perform in the real world and improved sit-to-stand capacity to a greater extent than CON in adults living with type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT06407245.

Aged

Assessing time to symptomatic progression, a patient-relevant efficacy endpoint, in the MARIPOSA study in non-small cell lung cancer.

INTRODUCTION: In the phase 3 randomized MARIPOSA study, amivantamab and lazertinib combination therapy demonstrated improved progression-free survival (PFS) and overall survival (OS) versus osimertinib in participants with previously untreated, epidermal growth factor receptor-mutated advanced non-small cell lung cancer. Time to symptomatic progression (TTSP) was introduced to assess clinical worsening and complement endpoints that investigate radiographic disease progression and patient-reported outcomes. TTSP provides an easily interpretable measure of disease-specific symptom worsening to further support patient experience. METHODS: In MARIPOSA, TTSP was quantitatively assessed as a secondary efficacy endpoint and defined as the time from randomization until participants experience disease-specific symptom worsening requiring a clinical intervention or treatment change, or death. To evaluate the impact of amivantamab and lazertinib on TTSP considering its established OS benefit against osimertinib, an exploratory analysis censoring death events was performed. RESULTS: At the final protocol-specified OS analysis (median follow up: 37.8 months), median TTSP was 43.6 months with amivantamab and lazertinib versus 29.3 months with osimertinib (hazard ratio [HR]: 0.69; 95% confidence interval [CI]: 0.57-0.83; p&#x202f;<&#x202f;0.0001). Amivantamab and lazertinib reduced deaths following a TTSP event compared to osimertinib. A strong correlation between TTSP and PFS or OS was observed. CONCLUSIONS: Amivantamab and lazertinib significantly delayed TTSP versus osimertinib. TTSP offers a clinician-validated measurement of disease-specific symptom worsening, capturing symptoms perceived by patients that prompt clinical action. TTSP is highly correlated with PFS and OS, providing complementary insights alongside traditional endpoints. TTSP enhances understanding of treatment benefit and supports informed clinical decision-making by integrating patient experience.

Humans