Lemon Balm (Calm)

INTRODUCTION: Therapeutic hypnosis appears to offer psychological and physiological benefits in various medical fields, but despite increasing interest, its value for anaesthesia remains inconclusive. METHODS: We searched for studies of any design in which hypnosis was used for any intervention requiring the presence of an anaesthetist, alone or in combination with any type of anaesthesia, on children and adults. Meta-analyses using random-effects models were stratified on hypnosis timing, when three or more randomised controlled trials reported on a similar outcome. Additional analyses were performed adding data derived from non-randomised controlled studies. The primary outcome was the use of hypnotics and opioids during the intervention. Secondary outcomes included all outcomes related to pain, anxiety or adverse events. RESULTS: We identified 142 studies that included 9238 patients (8319 adults, 919 children). Pre-intervention hypnosis decreased post-intervention visual analogue scale pain score (mean difference -0.88 cm, 95%CI -1.72 to -0.05) and anxiety (standardised mean difference -0.76, 95%CI -1.14 to -0.38). Per-intervention hypnosis decreased visual analogue scale pain intensity during the intervention (mean difference -1.14 cm, 95%CI -1.86 to -0.41) without impacting on post-intervention pain; decreased post-intervention anxiety (standardised mean difference -0.44, 95%CI -0.75 to -0.13); and lowered the risk of postoperative nausea and vomiting (risk ratio 0.43, 95%CI 0.25-0.74). Adding non-randomised controlled studies did not alter these results substantially. Evidence of the impact of pre- or per-intervention hypnosis on other outcomes, or of post-intervention hypnosis on any outcome, was lacking. DISCUSSION: Hypnosis may help reduce anxiety, alleviate pain during and after a procedure and lower the incidence of postoperative nausea and vomiting. However, despite the inclusion of more than 9000 patients in studies examining the use of hypnosis for anaesthesia, its impact on most outcomes remains unknown. Plain Language Summary: Hypnosis is sometimes used in medicine and may help people feel better in their mind and body. Some doctors are interest

OBJECTIVES: Confidence among surgeons is required for complex decision-making and surgical ability. However, surgical trainees' confidence is decreasing. This systematic review aims to explore factors that affect the confidence of surgical trainees. METHODS: A systematic review was performed following the PRISMA guidelines. Pubmed®, Embase™, Scopus, ClinicalTrials.gov and grey literature were searched for primary research on factors affecting surgical trainee confidence. RESULTS: Eleven studies were included. Key factors positively impacting trainee confidence were receiving regular positive feedback, working with a supportive trainer and having a calm working environment and effective team dynamic. The main factors negatively impacting trainee confidence were experiencing undermining behaviour from trainers and stressful, time-pressured environments. Female gender was also associated with reduced confidence. Greater confidence was associated with higher perceived performance. CONCLUSION: This work assimilates the factors impacting surgical trainees' confidence, which could guide training programmes to improve trainee self-confidence and therefore patient care.

To investigate mechanisms of change and/or mediators across psychosocial research for improving the wellbeing of people with dementia. Searches were conducted from August 2023-October 2024. The CASP and MMAT Tools were used for methodological quality assessment. Thirty studies were included. Mediating variables and mechanisms of change were identified at the individual, carer and process/system-level. Some individuals' variables included physical fitness, social engagement, memories of achievements and strengths, tailored activities according to interests, controlling for pain/psychopathology, expressing anger/grief/sense of humour, being involved in the care of pets, optimism, self-esteem, positive attitude toward aging, lower subjective age, and neuroticism. Carer-level influencing variables were burden, making adaptations at home, social care knowledge, medications, support groups, dyadic coping/religiosity, relationship quality. Process/system-level variables related to having a familiar/calm/secure place, regular and outdoor activities, horse and nature connection, being in the community/socialization/connectedness, therapist knowledge of dementia care/rapport, music, arts, life-storytelling, mindfulness, reminiscence about personal strengths/achievements for present and future goal-setting, and unstructured sessions. Person-centered care for living well with dementia must be evidence-based. We provide a scientific base for planning future interventions, health/care policies, and practices, by informing therapeutic targets that may improve the wellbeing of people with dementia.

153. J Drugs Dermatol. 2025 Jun 1;24(6):621-630. doi: 10.36849/JDD.8967. Practical Algorithm on Topical Treatment of Flaring Atopic Dermatitis (AD) With or Without Secondary Infection. Schachner LA, Hebert AA, Sidbury R, Andriessen A, Adzovic V, Gonzalez ME, Swanson E, Kwatra SG, Song EJ, West D, Lio P. Acute exacerbations or flares are a key characteristic of atopic dermatitis (AD), often associated with sleep deprivation, as well as experiences of stigmatization, social withdrawal, anxiety, and depression. Local skin colonization with Staphylococcus aureus (SA) is a key contributor to AD, particularly to AD flares. Treating SA-driven active AD, especially in cases where skin that is secondarily infected complicates management, calls for a carefully balanced approach that serves to calm AD activity and clear local infection and SA related colonization. The methodological approach included a systematic literature review to inform an expert panel before a face-to-face meeting to develop a practice-based algorithm for managing AD flares with or without secondary infection. A panel of nine experts in dermatology, including both Board-certified dermatologists and pediatric dermatologists, engaged in a discussion followed by an online review to refine the algorithm and to provide clear guidance on the topical treatment of flaring AD with or without AD skin that is secondarily infected. The algorithmic recommendations emphasize a need for therapy that addresses both skin inflammation and local SA colonization and/or infection, underscoring the unmet need for multi-targeted topical therapies such as zabalafin hydrogel, a novel approach under current investigation for persons with active AD, including flaring and secondary infected AD. This novel practice-based algorithm aims to improve outcomes for all AD patients, especially those with frequent flares or secondary infections and highlights the importance of balancing efficacy with antibiotic stewardship. Citation: Schachner LA, Hebert AA, Sidbury R, et al. Practical algorithm on topical treatment of flaring atopic dermatitis (AD) with or without secondary infection. J Drugs Dermatol. 2025;24(6):621-630. doi:10.3684

BACKGROUND: Managing cancer and living meaningfully (CALM) therapy is a psychosocial intervention designed to enhance the well-being of cancer patients; however, its impact on health-related outcomes in cancer patients remains unclear. AIMS: This study aimed to systematically synthesize current evidence to assess the impact of CALM therapy on health-related health outcomes and identify key features for optimizing the intervention. METHODS: An exhaustive search was conducted across seven databases from inception to July 5, 2024. Two reviewers separately evaluated the eligibility of studies, performed data extraction, and examined the methodological quality using the Cochrane's risk of bias tool. The certainty of evidence was evaluated using GRADE, and data analysis was conducted with Review Manager 5.4. The study protocol was registered with PROSPERO (CRD42024568561). RESULTS: Eleven studies (n = 1284) were included. CALM therapy showed significant improvements in psychological distress (MD = -2.43, 95% CI [-3.99, -0.86], p = 0.002), anxiety (SMD = -1.06, 95% CI [-1.78, -0.34], p = 0.004), depression (SMD = -0.65, 95% CI [-1.13, -0.17], p = 0.008), quality of life (SMD = 1.44, 95% CI [0.47, 2.40], p = 0.003), cancer-related fatigue (SMD = -3.54, 95% CI [-5.84, -1.23], p = 0.003), and sleep disturbance (SMD = -1.00, 95% CI [-1.86, -0.14], p = 0.02). However, its effects on alleviating the fear of cancer recurrence were not statistically significant. LINKING EVIDENCE TO ACTION: CALM therapy has demonstrated positive effects on psychological distress, anxiety, depression, cancer-related fatigue, sleep disturbance, and quality of life. However, evidence regarding its effects on the fear of cancer recurrence remains limited. While we explored potential sources of heterogeneity, no primary cause was identified. Our findings remained largely consistent after this exploration, but due to the observed heterogeneity, these results should still be interpreted with caution. Further high-quality randomized controlled trials with larger sample sizes are needed to confirm these findings and assess the long-term implications of CALM therapy. © 2025 The Author(s). Worldviews on

Erratum in Inquiry. 2026 Jan-Dec;63:469580261450809. doi: 10.1177/00469580261450809. Palliative care (PC) services are essential for cancer patients, particularly in low- and middle-income countries (LMICs), where cancer-related deaths are disproportionately high. Despite their significance, access to effective PC remains limited in many LMIC settings. This systematic review aims to identify strategies for implementing PC services for cancer patients in these regions, focusing on the challenges faced. A comprehensive search was conducted for peer-reviewed articles published between January 2004 and July 2024, utilizing the databases Web of Science, Scopus, PubMed, and Google Scholar. The Critical Appraisal Skills Program (CASP) assessment tool was employed to evaluate the quality of the studies following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for transparency. Out of approximately 966 818 articles retrieved, only 17 studies met the defined inclusion criteria. The findings highlighted effective strategies for delivering PC services in LMICs, including patient navigator-led programs, telemedicine, and home health care services. The review highlighted several interventions for PC services, including massage, Cancer and Living Meaningfully (CALM), and light therapies. However, it also identified significant challenges, such as the educational levels of caregivers, patient acceptance of PC services, logistical issues, medication side effects, and a preference for traditional healing practices. This systematic review highlights the critical need for effective PC services for cancer patients in LMICs, where cancer-related mortality rates remain alarmingly high. By synthesizing data from various studies, this analysis offers a comprehensive framework for developing successful palliative care initiatives in these regions. It emphasizes the importance of training caregivers of cancer patients to enhance their confidence in delivering palliative care services and counseling patients about the benefits of these services. Utilizing this information can help practitioners and policymakers improve palliative care services, u

BACKGROUND: Cancer patients, at both early and advanced stages, face complex bio-psycho-social-spiritual problems impacting their quality of life (QoL). Managing Cancer and Living Meaningfully (CALM) therapy is a psychotherapeutic approach that helps cancer patients find hope and meaning in life, thereby improving QoL. AIM: This study aimed to critically assess the effects of CALM therapy on the QoL in cancer patients. DESIGN: This was a systematic review and meta-analysis of randomised controlled trials (RCTs). METHODS: The main outcome was QoL, and the secondary outcomes were anxiety, depression, spiritual well-being, fatigue and sleep quality. Five English databases (PubMed, Embase, Scopus, Cochrane Library and ProQuest) and one trial registry site (Clinicaltrial.gov) were searched from their inception until March 2024. The pooled effect sizes were calculated using random-effects models and expressed as standard mean difference (SMD) or weighted mean difference (WMD). Review Manager 5.4 was used for data analysis. A sensitivity analysis was done by excluding one trial at a time to check the consistency of the results on QoL. The study protocol was prospectively registered on PROSPERO (CRD42023398655). RESULTS: Fifteen trials met the inclusion criteria for the systematic review and twelve for the meta-analysis, with a total of 1635 cancer patients. CALM therapy showed significant benefits on QoL (SMD = 1.97), spiritual well-being (WMD = 1.93) and sleep quality (SMD = -1.56) compared with usual care. It also reduced anxiety (SMD = -1.94), depression (SMD = -1.28) and fatigue (SMD = -5.86) significantly. The sensitivity analysis confirmed the stability of these results when each trial was removed one by one. CONCLUSION: CALM therapy may improve QoL, spiritual well-being, sleep quality and relieve anxiety, depression and fatigue in cancer patients. RELEVANCE TO CLINICAL PRACTICE: This therapy should be promoted clinically as a comprehensive psychotherapeutic approach in cancer care. REGISTRATION: CRD42023398655. © 2025 John Wiley & Sons Ltd.

INTRODUCTION: Despite increasing global migration, children from migrant backgrounds are underrepresented in physical activity research. This systematic review aimed to consolidate existing qualitative evidence on parental perceptions of the benefits, barriers, and facilitators of promoting physical activity and limiting sedentary behavior of their first- or second-generation migrant children aged 0-6 years. METHODS: Six electronic databases (Medline, CINAHL, PsycINFO, SPORTDiscus, Global, and Health EMBASE) were searched for qualitative peer-reviewed English language studies using terms covering migrants, parents, perceptions, physical activity, and sedentary behavior. Analysis was guided by the best-fit framework synthesis approach and the socio-ecological model. RESULTS: Database searches yielded 6059 unique records, with 33 studies included in this review. Key parent perceived benefits of physical activity were better health outcomes, development, and long-term outcomes and perceived benefits of sedentary behavior were education, health and development, and a parenting tool to keep children calm and occupied. Eight themes (25 sub-themes) across four levels of the socio-ecological model (primarily interpersonal and community level) were identified as barriers and facilitators of physical activity. Seven themes (14 sub-themes: primarily interpersonal) were identified for sedentary behavior. CONCLUSION: Parents from migrant backgrounds perceived that their young children experienced some unique barriers to physical activity and sedentary behavior. © 2025 The Author(s). Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation.

OBJECTIVE: This study aimed to evaluate the impact of non-pharmacological interventions on fear of cancer recurrence in patients with cancer by synthesizing evidence from various studies using the net meta-analysis (NMA) approach. Additionally, the study sought to rank the efficacy of these interventions. METHODS: Two investigators independently searched the PubMed, Cochrane Library, Embase, and Web of Science databases to identify randomized controlled trials(RCTs) that met the inclusion criteria. The search encompassed the period from the inception of the database to December 2023. The included studies were then subjected to a quality assessment, and a network meta-analysis was performed to evaluate and compare the effectiveness of the interventions. RESULTS: This study included 27 RCTs involving 3009 patients and examined seven types of non-pharmacological interventions. The NMA results indicated that, based on the Surface Under the Cumulative Ranking curve, Cancer and Living Meaningfully (CALM) was the most effective intervention (100 %), followed by Mindfulness Therapy (MT) at 76.5 % and Couples' Skills Training (CST) at 60.6 %. However, the league table results showed that, compared to the waitlist group, the effects of CALM [SMD = -4.83, 95 % CI (-5.93, -3.73)] and CST [SMD = -0.86, 95 % CI (-1.65, -0.07)] were significant, while MT [SMD = -1.52, 95 % CI (-3.46, 0.43)] did not reach statistical significance. Furthermore, CST was more effective than Cognitive Behavioral Therapy [SMD = -2.98, 95 % CI (-5.40, -0.56)]. CONCLUSION: The results of this study indicate that CALM is the most effective intervention for addressing mental health issues.

Polyvagal theory posits that habitually aggressive individuals might have an impaired capacity to calm after arousal, which has led to the investigation of Arousal-based biological indicators - "biomarkers" - of aggression, to identify individuals at high risk. The most popular approach in research examining (specifically reactive) aggression is the use of wearable technologies that can non-invasively measure heart rate variability (HRV), a cardiovascular phenomenon impacted by activation of the parasympathetic ("rest and digest") nervous system. But there is a problem: no one has systematically analyzed the results of these studies to determine if HRV is an effective predictor of reactive aggression. We surveyed an initial 705 articles, producing 48 effect estimates amenable to meta-analysis. Counter to predictions derived from polyvagal theory, the results reveal no correlation between HRV and reactive aggression. We discuss the implications of this novel finding for theory and practice, considering both the complexity of identifying effective biomarkers and the practical limitations driving methodological decisions in aggression research. We conclude that there is no empirical evidence supporting HRV as a valid biomarker of aggression. © 2024 The Author(s). Aggressive Behavior published by Wiley Periodicals LLC.

While healthy lifestyle behaviours are linked to better mental health, our understanding of how adherence to national recommendations affects outcomes is limited. This study investigates the relationship between adherence to Australian diet, physical activity, alcohol, and smoking guidelines and mental health outcomes in 182 adults experiencing psychological distress. By pooling data from both arms of a non-inferiority trial comparing lifestyle-based therapy to psychotherapy, we examined how adherence to national lifestyle guidelines and dietary components was associated with depression and anxiety outcomes. Greater diet quality (RR = 0.93), physical activity (RR = 0.51) and limited alcohol consumption (RR = 0.59) were linked to reduced risk of depression and anxiety, while ultra-processed foods were associated with higher risk (RR = 1.03). These findings highlight the importance of integrating lifestyle modification into mental health prevention and treatment and suggest that prescribing dietary behaviours based on national guidelines may offer practical mental health benefits.

BACKGROUND: Treatment expectancy is a key mechanism underlying placebo. While well-documented in psychopharmacology and psychotherapy, its role in lifestyle-based interventions for mental disorders is uncertain. Given the emerging role of lifestyle-based mental health care, a comprehensive evaluation of the role of treatment expectancy has not yet been explored, especially when compared to other more established therapies. The potential for genuine treatment efficacy to be masked by placebo response may bring into question the magnitude of effects of this treatment. METHODS: We sought to: 1) investigate the role of treatment expectancy as a moderator of depression treatment outcomes in a completed randomised controlled trial of psychotherapy versus lifestyle therapy (the CALM trial); and 2) provide guidance on measuring and reporting expectancy effects in future trials. CALM was a two-arm, parallel-group, non-inferiority randomised controlled trial, comparing lifestyle therapy (delivered by accredited dietitians and exercise physiologists) and psychotherapy (facilitated by psychologists). A total of 182 participants (91 per arm) experiencing psychological distress (equivalent to 'indicative depression') during the COVID-19 pandemic were randomised. We assessed associations of expectancy (measured prior to randomisation using the Credibility-Expectancy Questionnaire) with reductions in depressive symptoms (as measured by the PHQ-9). RESULTS: Expectancy scores did not differ between treatment groups at baseline (β = 1.14; 95%CI = -1.93, 4.22). Both arms reduced PHQ-9 between baseline and 8-weeks (lifestyle mean difference = -30.25%, SD = 58.23%; psychotherapy mean difference = -22.46%, SD = 66.87%). However, higher expectancy was associated with a greater reduction in depression only in the psychotherapy arm: for every 1-unit increase in expectancy score depressive symptoms reduced by an additional 3.21% for psychotherapy compared to lifestyle therapy (95%CI = -5.77, -0.65). CONCLUSIONS: In this study we showed that participants' expectations about treatment at enrolment were only associated with treatment response in psychotherapy. These findings highlight the ne

162. Int J Yoga Therap. 2026 Jan 14;35(2025):Article 12. doi: 10.17761/2025-D-25-00001. Embodied Affect and Cognition in Yoga Postures: A Randomized Crossover Trial. Telles S, Sharma SK, Kumar A, Gandharva K, Mishra P, Balakrishna A. A previous study reported an exclusive increase in positive mood states with backward-bending postures, with some changes common to both forward- and backward-bending postures, in 11 yoga beginners. To further determine any unique effects of forward- or backward-bending postures, the present trial examined six yoga postures in 64 yoga-experienced participants (mean age 22.81 ± 2.01; male-to-female ratio 24:40). We assessed mood states (Brief Mood Introspection Scale), relaxation (Relaxation State Questionnaire), and attention (Letter-Digit Substitution Test) before and after six yoga postures performed on 6 separate days in random order. There were two forward-bending postures (forward sitting, or seated forward bend, and forward standing, or hand-to-foot pose), two backward-bending postures (backward sitting, or camel pose, and backward standing, or half-wheel pose), and two control postures (control sitting, or easy pose, and control standing, or mountain pose), each done for 90 seconds. Both forward sitting/seated forward bend and forward standing/hand-to-foot increased peppy feelings and decreased drowsy feelings (p < 0.05 in all cases, repeated-measures ANOVA). Both backward sitting/camel and backward standing/half-wheel increased feeling calm and active. Forward sitting/seated forward bend increased feeling happy and content, whereas backward standing/half-wheel increased content and loving feelings. Control sitting/easy pose alone decreased feeling gloomy and drowsy and increased overall relaxation. All postures increased net attempts (suggesting enhanced attention) in the Letter-Digit Substitution Test, while forward standing/hand-to-foot alone decreased incorrect attempts (indicating enhanced accuracy). The results suggest that both forward- and backward-bending yoga postures have unique as well as common effects on mood states. Specific yoga postures may be selected to modify mood states, while research in clinical popu

Objective: The purpose of this study was to explore the effects of an acute dose of cannabidiol (CBD) on physical and mental health, as well as running performance in a group of runners. Methods: This study used a randomized, cross-over design where individuals were given CBD (CBD-T) or placebo (PLA-T) capsules on two separate occasions. During their first visit, the subjects consumed 300 mg of either placebo or CBD capsules and were then instructed to sit quietly for 2 h. Then, participants filled out a State Trait Anxiety Inventory (STAI) and completed measures of resting systolic (SBP) and diastolic blood pressure (DBP), heart rate (HR), blood lactate (BL), and heart rate variability (HRV). Next, participants completed a 2-mile treadmill run as fast as possible. During each run, HR, rating of perceived exertion (RPE), and BL were measured during and after the run. Participants completed a gastrointestinal (GI) symptom questionnaire immediately after the 2-mile time trial. Results: Participants (N = 12; 4 males, 8 females) averaged 25.5 years ± 3.34 years of age. Mean CBD-T reported increased feelings of calm (21% p = 0.04) and relaxed (22%, p = 0.02) when compared to PLA-T. There were no differences in the severity of GI symptoms, SBP, DBP, or HRV between the treatments. The CBD-T experienced an 8% reduction in average RPE at mile 1 of the run compared with PLA-T (p = 0.05). There was no significant difference in run performance time. Conclusions: An acute dose of CBD (300 mg) taken 2 h before a 2-mile run may potentially benefit runners in shorter distance competitions by increasing calm and relaxed feelings and reducing perceived effort at the halfway point without impairing performance or increasing gastrointestinal upset.

BACKGROUND: Rhomboid intercostal and sub-serratus plane (RISS) block is a novel nerve block technique that provides good analgesia, but overall research is scarce. This study aimed to investigate the effect of ultrasound-guided RISS block on postoperative analgesia and diaphragmatic excursion (DE) after video-assisted thoracic surgery (VATS) for lung cancer. METHODS: One hundred patients who underwent VATS lung resection participated in this study and were randomized to a RISS group (Group R) or a control group (Group C). Group R underwent ultrasound-guided RISS block with 0.25% ropivacaine hydrochloride 0.5 ml/kg immediately after surgery. Group C was given standard general anaesthesia, and patient-controlled intravenous analgesia (PCIA) was used in the postoperative period in both groups. The visual analogue scores (VAS) at rest and during movement at 2 hours(h), 24 h, and 48 h postoperatively were used as the primary outcome measures. Secondary outcomes included postoperative consumption of sufentanil; preoperative and postoperative left and right-sided DE during calm and deep breathing, and the occurrence of adverse effects such as postoperative nausea and vomiting (PONV), dizziness, somnolence, puncture site infection, and hematoma. RESULTS: At 2 h, 24 h, and 48 h postoperatively, patients in Group R had lower VAS scores at rest (median [Q1, Q3]: 1.00 [1.00, 1.00]; 1.00 [1.00, 1.00]; 0.00 [0.00, 1.00]) and during movement (2.00 [2.00, 3.00]; 2.00 [2.00, 2.00]; 2.00 [1.00, 2.00]) than those in Group C (resting: 2.00 [2.00, 2.00]; 2.00 [2.00, 2.00]; 1.00 [1.00, 2.00]; movement: 3.00 [3.00, 4.00]; 3.00 [3.00, 4.00]; 3.00 [2.00, 4.00]) (all P < 0.0001). Sufentanil consumption at 2 h, 24 h, and 48 h postoperatively was also significantly lower in Group R (P = 0.0002, P < 0.0001, P < 0.0001). Preoperatively, no significant difference in DE existed between the groups (P > 0.05). At 30 min post-extubation and 2 h and 24 h postoperatively, during both calm and deep breathing on both sides, Group R had significantly greater DE than Group C (P < 0.05). At 48 h postoperatively, the right-sided DE during calm breathing showed no significant difference between the groups

BACKGROUND: Wearable fitness technologies, like the Oura Ring (Oura Health Oy), provide physiological metrics, like sleep and heart rate data, to a growing user base of young adults. However, these technologies and connected mobile apps do not measure young adults' alcohol use that contributes to these metrics. Personalized feedback on the impact of alcohol on sleep and heart rate may boost motivation to reduce drinking among young adults. OBJECTIVE: For this pilot randomized controlled trial, we evaluated the acceptability, feasibility, and perceived effectiveness of a wearable personalized feedback intervention for alcohol reduction in young adults that integrated physiological and behavioral data. METHODS: Recruitment took place offline and online via open access websites. Participants (N=60) wore the Oura Ring for 6 weeks and completed daily behavioral smartphone diaries. Only the feedback group (n=30) had full access to the Oura Ring app and personalized feedback reports every 2 weeks, received from the study team. The app included daily feedback on sleep and cardiovascular recovery. Feedback reports combined Oura Ring and diary data to show trends of alcohol use alongside sleep and cardiovascular data. We used artificial intelligence-driven convergent mixed methods to evaluate self-assessed exit surveys and face-to-face exit interviews, including natural language processing and researcher-coded qualitative analyses with interviews. RESULTS: Half of participants (30/60, 50%) were men, 81.6% (49/60) were White, and they had a mean age of 22.02 (SD 1.98) years. Across both groups, the overall program was described as highly acceptable, feasible, and effective. Wearing the Oura Ring was highly acceptable and feasible. The smartphone diaries were moderately acceptable, moderately-highly feasible, and highly effective. The feedback reports were highly acceptable, feasible, and effective. Among feedback group participants, the Oura Ring and app were moderately effective. The feedback group participants also had high adherence using the app daily, and 80% (48/60) read all 3 feedback reports. Per natural language processing, the most common topic in the feedback in

BACKGROUND: Cognitive behavioral therapy (CBT) is recommended as the first-line treatment for insomnia; however, few patients have access to it. A new class of Food and Drug Administration (FDA)-regulated digital CBT treatments has the potential to address this unmet need. These treatments are ordered or prescribed by health care providers and are fully automated, delivering CBT directly to patients without human coaches. This trial builds upon promising earlier digital cognitive behavioral therapy for insomnia (CBT-I) research by using a decentralized design to recruit a sample with greater representation of the US general population, including individuals from lower socioeconomic status groups who often face greater barriers to care. OBJECTIVE: This decentralized trial evaluated the effectiveness of a fully automated digital CBT-I program (SleepioRx) for treating insomnia disorder compared with online sleep hygiene education (SHE) in a sample of participants recruited from across the United States. METHODS: A decentralized, parallel-group randomized controlled trial was conducted between November 2022 and August 2023. Participants were recruited nationally from across the United States, and a total of 336 adults aged 22 and older, diagnosed with the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) insomnia disorder via structured clinical interview, were allocated 1:1 to either digital CBT-I (SleepioRx) or online SHE. The primary end points were insomnia severity, assessed using the Insomnia Severity Index (ISI), and sleep diary measures of sleep onset latency (SOL) and wake after sleep onset (WASO) at 10 weeks, with follow-up assessments at 16 and 24 weeks postrandomization. RESULTS: Compared with SHE, SleepioRx showed statistically and clinically significant improvements on the ISI at posttreatment (10 weeks; Cohen d=0.60, P<.001), with effects sustained at follow-up (16 weeks; d=0.65, P<.001; and 24 weeks, d=0.77, P<.001). SleepioRx led to significant reductions in WASO at all time points (10 weeks, P=.003; 16 and 24 weeks, P<.001); however, effects on SOL were not statistically significant at an adjusted α (10 weeks, P=.01

BACKGROUND: The perioperative environment is complex and may be challenging for patients and guardians to navigate. The emotional burden and stressors inherent to the perioperative process commonly result in preoperative anxiety. Many studies have demonstrated the usefulness of virtual reality (VR) in various patient populations. OBJECTIVE: The aim of this study is to evaluate the impact of a VR-based preoperative education tool on anxiety levels in pediatric patients undergoing ambulatory ear, nose, and throat surgery, as well as in their guardians. METHODS: We performed a single-center prospective randomized controlled trial including children 6-12 years of age, presenting for ambulatory tonsillectomy and/or adenoidectomy, with or without bilateral ear tube insertion. The patients were randomized to receive VR instruction of the perioperative workflow or standard preoperative experience (non-VR). The primary outcome was patient and guardian preoperative anxiety, as measured by the 6-item State-Trait Anxiety Inventory. RESULTS: The study cohort included 107 patient-guardian dyads-51 in the intervention (VR) group and 56 in the control (non-VR) group. Baseline characteristics between the study and control groups were comparable; however, patients in the control group were more likely to report feeling upset compared to the VR group. The VR intervention was associated with reduced preoperative anxiety in patients and guardians compared to the control group. Patients exposed to the VR intervention had higher odds of feeling calm (OR 4.95, 95% CI 2.32-10.61; P<.001) and lower odds of feeling worried (OR 0.25, 95% CI 0.12-0.53; P<.001) compared to the control group. Similarly, guardians in the VR group had higher odds of feeling calm (OR 3.55, 95% CI 1.69-7.49; P=.001) and lower odds of feeling worried (OR 0.45, 95% CI 0.22-0.93; P=.03) compared to the control group. Both patients and guardians exposed to VR were significantly less likely to have moderate or high levels of preoperative anxiety than the control group (patients: OR 0.15, 95% CI 0.05-0.41, P<.001; guardians: OR 0.14, 95% CI 0.06-0.38, P<.001). CONCLUSIONS: VR exposure may be effective in reducing pedia

OBJECTIVE: This study examined feasibility, acceptability, and preliminary clinical impact of Veterans Affairs Coordinated Anxiety Learning and Management- Substance (VA CALM-S), a computer-assisted, transdiagnostic cognitive behavioral intervention for co-occurring anxiety and substance use disorders (SUDs) among veterans. METHODS: Veterans with co-occurring anxiety and SUDs were randomized to receive VA CALM-S (n = 14) or usual care (n = 12). Acceptability and feasibility were assessed via treatment completion rates and qualitative feedback. Changes in self-reported anxiety symptoms, substance use, and substance-related consequences were assessed at posttreatment. RESULTS: Eighty-five percent of participants completed all VA CALM-S modules. Qualitative feedback indicated the intervention was well-received and helpful. Moderate-to-large effect sizes were observed for VA CALM-S in reducing anxiety symptoms (d = 0.64), substance use (d = 0.69), and substance-related consequences (d = 0.34). Relatively smaller effect sizes were observed for the usual care condition in anxiety symptoms (d = 0.24), substance use (d = 0.12), and substance-related consequences (d = -0.46). CONCLUSIONS: Findings support the feasibility and acceptability of VA CALM-S for veterans with co-occurring anxiety and SUDs.

BACKGROUND: Caffeine is a well-known ergogenic aid that can enhance physical and cognitive performance. However, it often induces side effects, such as anxiety and overstimulation, which can be problematic in high-pressure sports like wrestling. L-theanine, a non-stimulant amino acid found in tea, may help mitigate these effects by promoting a calm yet focused mental state. This study aimed to investigate the acute effects of caffeine, L-theanine, and their combination on physical performance, cognitive function, and anxiety in elite male wrestlers. METHODS: In a double-blind, placebo-controlled, crossover design, 12 elite male wrestlers (21.8 ± 2.1 years) completed four test sessions under randomized conditions: placebo (PLA), caffeine (CAF; 3 mg/kg), L-theanine (THE; 3 mg/kg), and caffeine + L-theanine (CAF+THE; 3 mg/kg each). After 60 minutes, athletes performed the wall-squat test, vertical jump height (VJH), medicine ball throw (MBT), handgrip strength, and the Specific Wrestling Fitness Test (SWFT). Cognitive function was assessed pre- and post-SWFT using a computerized Stroop test. Anxiety was assessed using the State-Trait Anxiety Inventory (STAI), and side effects were recorded. RESULTS: CAF+THE outperformed PLA in wall-squat time (p = 0.001), MBT (p = 0.005), VJH (p = 0.011), and grip strength (p = 0.004). SWFT throw count was highest in CAF+THE versus all other conditions (p < 0.001). Post-SWFT Stroop reaction time was faster in CAF+THE than PLA (p = 0.004) and THE (p = 0.036), and accuracy was also higher (p = 0.009 vs PLA). CAF alone increased state anxiety compared to PLA (p = 0.021), while CAF+THE reduced anxiety to below placebo levels (8% incidence vs 33%). Trait anxiety was lower in CAF+THE compared to CAF (p = 0.018). The prevalence of caffeine-induced tachycardia (92%) was notably reduced under CAF+THE (17%). CONCLUSION: CAF+THE (3 mg/kg each) enhances elite wrestlers' strength, endurance, cognitive speed, and accuracy while reducing anxiety and physiological side effects commonly associated with caffeine alone. This combination represents a safe, practical supplement strategy for combat sports athletes who must maintain explosive performance

OBJECTIVE: This study aims to investigate the impact and molecular mechanism of ELAVL1 in promoting macrophage M1 polarization in Crohn's disease (CD) by upregulating S100A8 expression. METHODS: Peripheral blood mononuclear cells (PBMCs) from CD patients were collected to assess the expression of S100A8 and ELAVL1. The effect of ELAVL1/S100A8 on THP1 derived macrophage polarization and pro-inflammatory mediator secretion were evaluated via siRNA silencing and rescue experiments. RNA-binding protein immunoprecipitation (RIP) and RNA pull-down assays validated the interaction between ELAVL1 and S100A8. RESULTS: Both S100A8 and ELAVL1 were significantly overexpressed in CD patients. Knockdown of S100A8 or ELAVL1 in M1-polarized macrophages marked reduced the expression of M1 biomarkers (CD80, CD86) and pro-inflammatory mediators. However, S100A8 overexpression reversed the inhibitory effects of ELAVL1 knockdown on M1 polarization, thereby promoting the M1 polarization and inflammatory response. RIP and RNA pull-down assays confirmed that ELAVL1 directly binds to S100A8 mRNA to regulate its expression. CONCLUSION: ELAVL1 promotes M1 polarization of macrophages to exacerbate intestinal inflammation in CD via up-regulating S100A8 expression. These findings highlight the ELAVL1/S100A8 axis as a potential therapeutic target or diagnostic biomarker for managing CD. Plain Language Summary: Crohn’s disease (CD) is a chronic condition where the immune system mistakenly attacks the digestive tract, causing severe inflammation. A specific type of immune cell, called a “macrophage,” acts like a double-edged sword: while it usually protects us, in CD, it can become overactive (known as M1 polarization) and release harmful chemicals that damage the gut.Our study identified a new biological “switch” involving two molecules, ELAVL1 and S100A8, that controls this overactive state. We found that in patients with CD, ELAVL1 levels are high and act like a stabilizer for S100A8, preventing it from breaking down. This buildup of S100A8 signal macrophages to stay in a highly aggressive, pro-inflammatory state.By using laboratory techniques to turn off this ELAVL1/S100A8 switch, we succe

In natural agricultural environments, plant disease monitoring faces significant challenges, including a highly uneven (long-tail) distribution of disease species, tiny scales of early-stage lesions, and complex, variable backgrounds. These factors hinder the ability of existing lightweight models to balance detection accuracy and computational efficiency. To address these issues, this paper proposes a detection scheme driven by the synergy of data distribution reshaping and model architecture optimization. At the data level, we propose the CALM-Aug augmentation strategy. Based on the statistical distribution characteristics of disease categories, this strategy utilizes object-level copy-paste logic to specifically compensate for the feature shortcomings of rare disease samples. It introduces a teacher-guided screening mechanism and employs accept-reject sampling to ensure the pathological consistency of the augmented samples, thereby alleviating the model's inductive bias toward head categories. At the model architecture level, using YOLOv11 as the baseline, the YOLO11-ARL model adapted to agricultural scenarios is constructed. It enhances sensitivity to early point-like disease spots through Efficient Multi-Scale Convolutional Pyramids and lightweight decoupled detection heads. Furthermore, a Layer-wise Adaptive Feature-guided Distillation Pruning (LAFDP) algorithm is utilized to extract a lightweight version, YOLO11-ARL-PD, achieving a significant reduction in parameters and computational cost. Experimental results on the PlantDoc dataset show that the final model achieves a precision of 89.0% and an [email protected] of 85.3%. Compared to the baseline model YOLOv11n, YOLO11-ARL-PD improves precision and average precision by 7.7 and 2.6 percentage points, respectively, while reducing parameters by 51.93% and weights by 46.15%. Cross-dataset tests prove the good generalization performance of the proposed method. This study indicates that, under lightweight constraints, jointly optimizing the training distribution and model architecture is an effective way to improve plant disease monitoring and to support the edge deployment of smart crop-protection systems. All resourc

BACKGROUND: In cardiac arrest management, cognitive aids provide prompts to encourage recall of critical information, which may improve clinical performance. Whether cognitive aids influence provider workload, cognitive load, teamwork dynamics, or leadership during cardiac arrest remains unknown. In this study, we evaluated the effect of using a multi-faceted decision support system with augmented reality-based cognitive aids (i.e. InterFACE-AR) vs. the American Heart Association (AHA) Pediatric Advanced Life Support (PALS) pocket card on provider workload and cognitive load, teamwork, and leadership during simulated pediatric cardiac arrest. METHODS: We conducted secondary analysis of data collected from a prospective, randomized controlled trial comparing the use of the InterFACE-AR system to the AHA PALS pocket card during simulated pediatric cardiac arrest. Participants were recruited in groups of 3 to perform the roles of team leader, medication nurse, and documenting nurse. All teams completed a 12-min simulated cardiac arrest scenario. Provider workload (NASA-RTLX) and cognitive load (Paas score) were captured from participants after the scenario. Teamwork (TEAM score) and leadership performance (CALM score) were assessed via video review. RESULTS: A total of 18 simulation sessions were analyzed (Control: n = 9; InterFACE-AR: n = 9), involving 54 participants in total. Team leaders using the InterFACE-AR system had lower RTLX (mean difference [MD]: -15.0; 95% confidence interval [CI]: -27.0 to -4.6, p = 0.022) and Paas score (MD: -2.4; 95%CI: -3.6 to -1.4, p < 0.001), while documenting nurses showed similar reductions (RTLX -13.7, 95%CI: -26.7 to -0.4, p = 0.049; Paas -1.6, 95%CI: -2.8 to -0.1, p = 0.046) compared with those using PALS pocket card. Medication nurses demonstrated no statistically significant differences in RTLX (p = 0.098) or Paas score (p = 0.194). Teams using the InterFACE-AR system achieved significantly higher TEAM scores compared to those using PALS pocket card only (39.2 vs 35.8, MD: 3.4, 95%CI: 0.8 - 5.9, p = 0.030). CALM scores did not differ significantly between groups. CONCLUSION: Use of an AR-based decision support system durin

Background: Dementia is one of the most common diseases of the elderly worldwide. Sharing experiences of caring for patients with dementia with other carers is essential to improve the quality of care, promote better outcomes, and learn from others. Aim: to explore nurses' experiences of working with patients with dementia in Lithuanian supportive treatment and nursing hospitals. Methods: A qualitative descriptive design was employed in this study, with data collected through semi-structured interviews. Nurses with direct experience caring for patients with dementia in supportive treatment and nursing hospitals were recruited through purposive sampling. This sampling strategy was chosen to ensure that participants could provide rich, contextual, and experience-based insights into the phenomenon under investigation. Open-ended questions were divided into three themes: 1. Identifying nursing needs. 2. Care for people with dementia. 3. Patient behavior management and situation management. To ensure methodological rigor and transparency, the Consolidated Criteria for Reporting Qualitative Research (COREQ) were applied throughout the study's planning, data collection, and analysis processes. Results: Nine nurses working in three different Lithuanian hospitals participated in the study. Theme 1: respondents reported that the needs of patients with dementia depend on their previous lifestyle and hobbies, as well as on essential physiological needs such as eating and drinking, bathing and personal hygiene, and the absence of pain. Theme 2: All participants emphasized that ensuring a safe environment is crucial for people with dementia. Theme 3: When faced with inappropriate patient behaviour, nurses attempt to calm the patient, speak gently, provide distraction, or, when necessary, temporarily separate the patient from others. Additional actions include administering medication and stabilizing the patient. Overall, these findings illustrate that dementia care requires continuous emotional presence, situational judgment, and adaptation to each patient's individual needs. Conclusions: Patients with dementia require highly individualized care focused on nutrition, hygiene,

INTRODUCTION: Followership refers to the active, relational behaviors individuals enact when supporting, shaping, or influencing leadership from positions without formal authority. Although leadership dominates health professions curricula and scholarship, followership remains comparatively underexamined. This qualitative study explores how fourth-year medical students conceptualized and practiced followership during a high-fidelity, military medical simulation. METHODS: Seventeen medical students participated in semi-structured interviews within three weeks of completing the exercise. Interviews focused on students' experiences with leadership and followership during the exercise. Transcripts were analyzed using thematic analysis informed by a constructivist orientation to understand how students made meaning of their experiences. RESULTS: Three interrelated themes were constructed describing how students perceived and enacted followership during the simulation: (1) anticipating and providing proactive support for leaders; (2) knowing when to step up, step back, and speak up; and (3) maintaining calm and promoting team morale during stress. Students emphasized that followership was not passive obedience but a practice that influenced team performance, leader effectiveness, and psychological safety. Many also recognized how their followership behaviors shaped their leadership development, reinforcing the interdependence of these roles. DISCUSSION: Findings offer insight into how learners conceptualize and enact followership in high-fidelity simulation environments. Recognizing followership as distinct from leadership and teamwork, this study contributes to a more precise understanding of how trainees develop within team-based healthcare settings.

BACKGROUND: Dog bite injuries pose a substantial public health burden worldwide. Environmental and acoustic stressors may contribute to dog behavioral dysregulation. However, there are as yet no population-level studies evaluating whether the incidence of dog bites increases during periods of armed conflict. The present study was conducted in Israel where the population is routinely exposed to an episodic pattern of high-intensity conflicts (escalation) alternating with periods of calm (de-escalation), providing a unique natural experiment to examine the effect of environmental stressors on population-level modifiers of injury risk. METHODS: This nationwide retrospective observational study covered the decade from 2014 to 2025. Healthcare-encounter data were used to capture dog bite-related diagnoses in both hospital and community settings. Exposure to armed conflict-related environmental stress was operationalized using the number of civil defense sirens per month, categorized as none (0), low (< 500), or high (≥ 500) and aggregated by geographic region (North, Center, South). Monthly dog bite counts were modeled using negative binomial regression adjusted for region, seasonality, age group, sex, and socioeconomic status. Secondary outcomes were hospitalization within 7 days and surgical intervention within 30 days, reflecting injury severity. RESULTS: A total of 63,285 dog bite-related encounters were identified. Compared to months with no sirens, adjusted dog bite incidence increased by 15% during low-exposure months (incidence rate ratio [IRR] 1.15, 95% CI 1.13-1.18) and by 33% during high-exposure months (IRR 1.33, 95% CI 1.28-1.37), demonstrating a graded exposure-response association. High exposure was associated with increased odds of surgical intervention within 30 days (OR 1.09, 95% CI 1.02-1.16; P = 0.013). CONCLUSIONS: This study provides the first population-level evidence linking armed conflict-related environmental stressors to increased dog bite incidence, using a quantitative graded exposure measure rather than a binary conflict-period definition. Dog bite prevention and healthcare preparedness should be taken into consideration in civilian inju

OBJECTIVE: Encephalitozoonosis is a widespread, common disease in rabbits that also bears significance as a potential zoonosis. The aim of the study is to analyse encephalitozoonosis in terms of diagnosis and treatment based on a retrospective evaluation of patient data. MATERIAL AND METHODS: 107 cases of rabbits with a suspected diagnosis of encephalitozoonosis presented at a university clinic between 2013 and 2022, were retrospectively evaluated. The cases were reviewed with regard to the form of encephalitozoonosis, husbandry, feeding, diagnosis, therapy and outcome. RESULTS: The housing systems - indoor versus outdoor housing, individual versus group housing - and the recent integration of an animal into the group did not exert statistically significant effects as predisposing factors. Clinically, encephalitozoonosis manifested itself in the central nervous system in 63.6% (n=68) of cases. The average age of animals with the ocular form was significantly lower (p<0.001) at 23.7 months, and that of animals with the renal form was higher than the average age of the entire population of diseased animals examined, with a mean of 71.4 months. When comparing the outcomes of 84 rabbits, 29.8% (n=25) showed improvement, 44.0% (n=37) stabilised and 28.2% (n=22) died or had to be euthanised. The IgG titre was significantly more frequently elevated (>1:5120) in the deceased or euthanised rabbits, at 50.0% (n=6). CONCLUSIONS AND CLINICAL RELEVANCE: The present study found no influence of husbandry parameters with regard to encephalitozoonosis. There was a correlation between age and form of the disease. The detection of antibodies played a central role in diagnosis, but only allowed for a presumptive diagnosis. Fendendazole, analgesia, anti-inflammatory drugs and supportive measures were used for treatment. Such measures included a calm and stress-free environment and physiotherapy for the central nervous form, and ensuring hydration for the renal form. In around 70% of cases, an improvement or stabilisation of the condition was achieved. Publisher: Die Enzephalitozoonose ist eine bei Kaninchen weit verbreitete Krankheit, die zudem als potenzielle Zoonose von Bedeutung

BACKGROUND: Transcranial electrical stimulation (TES) has limited spatial focus and depth penetration, constraining its therapeutic efficacy. Intersectional Short-Pulse (ISP) stimulation was developed to overcome these limitations by delivering rapidly switching pulses that can be temporally integrated by neuronal membranes. Here, we aimed to establish the biophysical basis of ISP-induced temporal summation and to test whether this mechanism enables effective brain modulation in vivo. METHODS: We combined finite-element modeling, cadaver measurements (n = 2 human cadavers), and biophysically realistic NEURON simulations to characterize the spatial and temporal properties of ISP-induced electric fields. In vivo whole-cell patch-clamp recordings were performed in the rat somatosensory cortex (female Wistar rat) to test the membrane-level integration of sequential electric field pulses. Functional efficacy was evaluated using closed-loop ISP stimulation in a hippocampal kindling model of temporal lobe epilepsy in male Long-Evans rats (n = 11 animals, >500 induced seizures analyzed across conditions). RESULTS: Here we show that neurons integrate sequential ISP pulses in a non-vectorial, temporally accumulative manner, consistent with membrane-level charge integration rather than extracellular field superposition. ISP and conventional TES simulations produced similar instantaneous field magnitudes, but ISP stimulation resulted in more uniform neuronal excitability across brain depths. Closed-loop ISP stimulation significantly outperformed conventional TES in reducing seizure duration and severity. ISP reduced hippocampal seizure duration by 45% and 35% compared to SHAM stimulation and conventional TES, and significantly reduced motor seizure severity. CONCLUSIONS: ISP stimulation provides a non-invasive neuromodulation approach that enhances deep brain engagement through rapid, temporally structured pulse sequences. These findings demonstrate effective seizure suppression in a rodent model and support the translational potential of ISP for disorders involving pathological neural dynamics. Plain Language Summary: Epilepsy is a disorder in which sudden bursts of abnor

AIMS: Implantable tibial nerve neuromodulation (ITNM) represents a minimally invasive intervention for urgency urinary incontinence (UUI). This study evaluated the 3-year cost-utility of ITNM with an external wearable battery (Revi System) versus conservative treatments (behavioral ± pharmacotherapy) from a US payer perspective. MATERIALS AND METHODS: A cohort state-transition (Markov) model with annual cycles compared ITNM to conservative treatment modalities (behavioral ± pharmacotherapy). ITNM clinical parameters were derived from the OASIS pivotal trial (N = 150); parameter uncertainty was propagated via 20,000 Monte Carlo simulations. Health states captured responder and non-responder status with permitted transitions, rescue interventions (onabotulinumtoxinA, sacral neuromodulation, percutaneous tibial nerve stimulation), and downstream event modules (falls, urinary tract infection, incontinence-associated dermatitis, depression, cognitive decline/dementia, and nursing-home entry). Costs and quality-adjusted life-years (QALYs) were discounted at 3% annually and expressed in 2025 US dollars. Parameter uncertainty was assessed using probabilistic sensitivity analysis (PSA; 20,000 simulations) and tornado analysis. RESULTS: ITNM was both more effective and less costly than behavioral ± pharmacotherapy. Mean 3-year costs were $39,308 versus $43,737 (ΔCost = -$4,428), with mean QALYs of 2.188 and 1.940, respectively (ΔQALY = +0.249). The incremental cost-effectiveness ratio was -$17,818/QALY (dominant). Incremental net monetary benefit at $40,000/QALY was $14,369, with 100% probability of cost-effectiveness across thresholds from $20,000-$150,000/QALY. Key value drivers were responder utility and fall-related parameters. LIMITATIONS: The analysis adopts a US payer perspective with direct medical costs only. Some event risks were applied from population-level sources and may not fully capture patient-level heterogeneity. The 3-year base-case horizon may miss longer-term durability effects, though extended-horizon scenarios support consistent findings. CONCLUSIONS: Over 3 years, ITNM with an external wearable battery improves quality-adjusted survival and lowers

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has now become a major global health concern. Lifestyle modifications are the first line of treatment; however, their effectiveness is often limited. Silymarin extracted from Silybum marianum is effective and well tolerated in patients with liver disorders. This study aimed to assess the effect of administration of silymarin along with lifestyle changes on lowering liver enzymes in patients with NAFLD and metabolic syndrome in a real-world setting. METHODS: Patients enrolled in this observational study were prescribed standard of care (diet and physical exercise) and one capsule of 140 mg of silymarin thrice daily for 6 months. Laboratory tests, non-invasive tests, ultrasonography, quality of life questionnaire, lifestyle changes and safety were assessed at 3-month and 6-month visits. RESULTS: Of 360 patients enrolled in the study, 315 (88%) completed the study. At baseline, aspartate transaminase (AST), alanine transaminase (ALT) and gamma-glutamyl transferase (GGT) levels were elevated in 45%, 90% and 47% of patients, respectively. By end of study, 45% (148/328) of patients achieved normalization in at least one enzyme (AST: 42%, ALT: 34%, GGT: 28%), and overall, 78% of patients showed reduction in levels for at least one liver enzyme. Enzyme levels including AST, ALT, and GGT, underwent a clinically relevant decrease (>30%) in 42%, 40%, and 34% of patients, respectively. Silymarin was well tolerated with no serious side-effects. CONCLUSION: Silymarin combined with lifestyle modifications is a safe and effective treatment option for reducing and normalizing liver enzyme levels in patients with NAFLD and associated metabolic syndrome. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT05051527. Plain Language Summary: WHAT WAS THIS STUDY ABOUT? Many people today live with fat building up in their livers, a condition called NAFLD. It often shows up along with metabolic syndrome (MetS), which means having health problems such as high blood pressure, high blood sugar or extra body weight. People who have both NAFLD and MetS are at a higher risk of developing diabetes, heart issues or liver d