Search Results (10,184)

Citrullus colocynthis (L.) Schrad., a drought-tolerant member of the Cucurbitaceae family, has been used in traditional medicine for centuries and has recently attracted increasing interest because of its potential pharmacological, agricultural, and ecological applications. This review examines current information on the plant’s distribution, ethnomedicinal uses, phytochemical composition, biological activities, applications in poultry, and ecological significance. Its bioactive constituents include cucurbitacins, flavonoids, phenolic compounds, alkaloids, glycosides, fatty acids, and tocopherols. These compounds have been associated with anticancer, antidiabetic, antimicrobial, antioxidant, anti-inflammatory, neuroprotective, hepatoprotective, and other biological activities, although most of the available evidence comes from in-vitro and preclinical studies. Initial findings also indicate that the plant may have value as a phytogenic feed additive in poultry and as a drought-tolerant species for soil stabilization, rangeland rehabilitation, and desertification control. However, the practical application of these findings is still constrained by differences in research methods, variation in phytochemical composition, limited clinical evidence, and the plant’s narrow therapeutic window and dose-dependent toxicity. Consequently, its therapeutic effectiveness and suitability for routine agricultural use cannot yet be established with certainty. Future research should focus on phytochemical standardization, quality control, thorough toxicological assessment, mechanistic studies, and well-designed clinical and animal trials using standardized preparations. Collectively, the available evidence indicates that C. colocynthis is a promising source of bioactive compounds with potential pharmaceutical, veterinary, and ecological applications, although rigorous scientific validation is required before its safe and effective utilization can be recommended. Full article

Background: Cervical cancer remains a major public health concern worldwide, particularly in low- and middle-income countries. Limited knowledge regarding cervical cancer prevention and elevated anxiety levels may hinder women’s participation in preventive measures. Mindfulness-Based Social–Emotional Learning integrates mindfulness practices with social–emotional learning strategies and may enhance health knowledge while reducing anxiety. Materials and Methods: A quasi-experimental pretest–posttest non-equivalent control group design was conducted among 80 women attending gynecological outpatient clinics in Egypt. Participants were assigned to a study group (n = 40) and a control group (n = 40). Data were collected using a structured interview questionnaire, a cervical cancer knowledge questionnaire, and the Beck Anxiety Inventory (BAI). The study group received an eight-week MBSEL intervention incorporating mindfulness exercises, social–emotional learning activities, and cervical cancer education, while the control group received routine health education. Pre- and post-intervention assessments were performed. Results: Baseline characteristics were comparable between groups. Following the intervention, the study group had significantly higher mean knowledge scores regarding cervical cancer prevention, with mean knowledge scores increasing from 38.71 ± 10.41 to 66.25 ± 8.95 compared with 42.09 ± 15.95 in the control group (t = 8.355, p < 0.001). Good knowledge levels increased from 2.5% to 35.0%, while poor knowledge declined from 62.5% to 0.0%. Anxiety levels significantly improved in the study group, with mean BAI scores decreasing from 38.68 ± 6.32 to 22.20 ± 3.91 compared with 34.28 ± 9.53 in the control group (t = 7.414, p < 0.001). Low anxiety increased from 2.5% to 62.5% in the study group compared with 7.5% to 12.5% in the control group, and severe anxiety was eliminated from 27.5% to 0.0% in the study group compared with 32.5% to 22.5% in the control group after the intervention. Conclusions: The MBSEL approach effectively enhanced women’s knowledge regarding cervical cancer prevention and significantly reduced anxiety levels. Integrating mindfulness practices with social–emotional learning and health education appears to strengthen cognitive engagement and emotional regulation. Clinical Trial Registration: Registered in accordance with WHO and ICMJE standards (Trial number: PACTR202605512267205). Registration date: 29 May 2026. Full article

Objective: We aimed to evaluate whether deep neuromuscular blockade (DNMB) improves surgical conditions and facilitates low-pressure pneumoperitoneum compared with moderate neuromuscular blockade (MNMB) during minimally invasive surgery. Data Sources: PubMed/MEDLINE, EMBASE, Cochrane CENTRAL, Scopus, Web of Science, and LILACS were searched from inception through May 2026. Study Selection: Randomized controlled trials comparing DNMB versus MNMB in adults undergoing laparoscopic or robot-assisted surgery were included. Data Extraction: Two reviewers independently screened studies, extracted data, and assessed risk of bias using the revised Cochrane Risk of Bias tool (RoB 2). Certainty of evidence was evaluated using the GRADE approach. Primary Outcomes: Primary outcomes were surgical workspace quality and intra-abdominal pressure requirements. Secondary Outcomes: Secondary outcomes included postoperative abdominal pain at 24 h and referred shoulder pain. Data Synthesis: Seventeen randomized controlled trials involving 1512 patients were included. DNMB consistently improved surgical workspace conditions and facilitated lower pneumoperitoneum pressures compared with MNMB. Pooled analyses additionally suggested reductions in postoperative abdominal pain and referred shoulder pain in selected studies, although postoperative outcomes demonstrated greater heterogeneity across procedures and perioperative protocols. Conclusions: Current evidence suggests that the principal clinical value of DNMB during minimally invasive surgery is optimization of surgical exposure and facilitation of low-pressure pneumoperitoneum strategies. Benefits related to postoperative abdominal pain may occur in selected settings but appear less consistent across procedures. Full article

Endometrial cancer is increasingly diagnosed in patients who have not yet completed childbearing. For carefully selected patients with grade 1 endometrioid endometrial carcinoma confined to the endometrium, fertility-sparing treatment (FST) can preserve reproductive potential but requires rigorous histologic surveillance. In eligible patients, oral progestins and/or the levonorgestrel-releasing intrauterine system (LNG-IUS) remain the mainstay of fertility-sparing treatment, with hysteroscopic lesion resection incorporated in selected cases. Obesity, polycystic ovary syndrome, abnormalities in glucose metabolism, molecular subtype, and primary or acquired progestin resistance collectively contribute to heterogeneity in treatment response and the risk of recurrence. This narrative review critically integrates current guidelines, randomized controlled trials, prospective studies, retrospective cohorts, and early exploratory evidence to evaluate the biological rationale, clinical positioning, efficacy, safety, and maturity of evidence for progestin-based therapy, metabolic interventions, combined endocrine approaches, molecularly guided strategies, and exploratory immunotherapeutic approaches. We further propose an integrated clinical pathway encompassing candidate selection, molecular assessment, response evaluation, transition to pregnancy, retreatment after recurrence, and timely conversion to definitive surgery. Importantly, this review distinguishes guideline-supported approaches from adjunctive, investigational, and exploratory strategies. Major evidence gaps include inconsistent definitions of treatment response, limited prospective molecularly stratified data, uncertain reproductive safety of emerging systemic therapies, and insufficient long-term data on pregnancy outcomes and offspring. Full article

Background/Objectives: Antibiotics are the recommended first-line therapy for acute uncomplicated lower urinary tract infections (cystitis), but antibiotic resistance and tolerability concerns require antibiotic-sparing strategies. This study evaluated D-mannose as a stand-alone alternative. Methods: This multicenter, randomized, controlled, double-blind study compared D-mannose to fosfomycin in women aged 18–70 with cystitis. Clinical cure (CC) was assessed using the Acute Cystitis Symptom Score (ACSS) up to day 8, with non-inferiority tested at the 15% margin. Post hoc analytical approaches accounted for potential bias due to low sample sizes and missing values. Results: The study randomized 118 patients. At baseline, severe symptoms (ACSS ≥ 12) were more frequent in the D-mannose group compared to fosfomycin (32.8% vs. 22.8%). Efficacy analyses were performed on the per-protocol set (D-mannose: N = 57; fosfomycin: N = 54). Median time to CC was 5.0 days (D-mannose) and 3.0 days (fosfomycin) overall, and 4.0 days vs. 3.0 days in the subgroup of moderate disease severity. The point estimate for the CC rate difference on day 8 (−10.1%) favored fosfomycin but was within the non-inferiority margin. Due to wide confidence intervals, non-inferiority was not statistically confirmed. The post hoc analysis yielded smaller confidence intervals with estimated CC rates of 84.2% (D-mannose) vs. 83.5% (fosfomycin) on day 8 and statistically demonstrated the comparability of both treatments. Recurrence rates were similar (13.2% vs. 13.3%), and there was no statistically significant difference for additional antibiotic use (19.3% vs. 11.1%). Investigators and patients favored D-mannose over fosfomycin for tolerability, and gastrointestinal adverse events were less frequent (9.8% vs. 24.6%). Conclusions: Post hoc analysis indicated that D-mannose treatment is comparable to fosfomycin in uncomplicated cystitis in line with the prespecified non-inferiority criteria. These findings warrant confirmation in an adequately powered trial but suggest that D-mannose is a promising alternative to antibiotics given its favorable risk–benefit ratio. Full article

Botulinum toxin, once known only as the cause of botulism, has become a versatile therapeutic agent whose use in children now extends across many medical and surgical specialties. This narrative review synthesises the clinical use of botulinum toxin in patients up to eighteen years of age. We describe its pharmacology, the non-interchangeable commercial preparations, and the weight-based dosing and safety principles specific to childhood, then examine its applications by organ system. Gastrointestinal uses include functional constipation and internal anal sphincter achalasia, persistent obstruction after surgery for Hirschsprung disease, anal fissure, and achalasia. Urological uses centre on neurogenic and idiopathic detrusor overactivity and on sphincter-directed injection for dysfunctional voiding. Neurological uses are dominated by cerebral palsy spasticity and, on considerably weaker evidence, dystonia, while head and neck uses include sialorrhoea, congenital muscular torticollis, and strabismus. We also address neonatal brachial plexus palsy together with hyperhidrosis and aesthetic use in adolescents. The evidence supporting these uses is markedly uneven. Randomised controlled trials exist for only a small number of paediatric indications, chiefly spasticity in cerebral palsy, neurogenic detrusor overactivity, and chronic sialorrhoea, whereas most remaining applications rest on observational cohorts, small case series, or extrapolation from adult practice, and we grade the certainty of evidence separately for every indication. Only a few indications are formally approved, and most remain off-label, though increasingly supported. Botulinum toxin is a reversible and generally safe adjunct, but rigorous paediatric trials are still needed. Full article

Background: Raynaud’s phenomenon (RP) may occur in the pediatric age span, sometimes representing the forerunner of devious underlying conditions. Objective: To investigate the prevalence of vitamin D deficiency in a single-center cohort of children and adolescents with idiopathic RP and evaluate changes in RP severity following cholecalciferol supplementation. Patients and Methods: Sixty-one children and adolescents with RP regularly followed at the pediatric rheumatology unit of our University between 2010 and 2025 were retrospectively evaluated. Clinical, laboratory, and nailfold videocapillaroscopy (NVC) findings were collected at baseline; patients were periodically examined for a mean investigation period of 3 ± 1.6 years. RP severity was assessed using the 2-week Raynaud’s Condition Score (RCS). Patients found to have serum 25-hydroxyvitamin D levels < 20 ng/mL received cholecalciferol supplementation for at least 12 weeks. Results: Nineteen out of 61 patients with RP (31.1% of the cohort) had vitamin D deficiency, while other laboratory parameters including inflammatory markers, complement fractions, liver and renal function tests, lipid profile, and autoimmune panel were non-informative. Univariate analysis demonstrated significant differences between vitamin D-deficient and non-deficient patients in terms of mean RP duration (p = 0.0002), baseline 2-week RCS (p = 0.0001), lupus-like anticoagulant positivity (p < 0.001), NVC pattern (p < 0.001), pain visual analogue scale (VAS) (p = 0.0001), and global quality of life VAS (p = 0.0001). After adjustment for age and sex, baseline 2-week RCS remained significantly associated with vitamin D deficiency. In addition, RCS significantly decreased during follow-up among vitamin D-deficient patients who received supplementation of cholecalciferol. Conclusions: Vitamin D deficiency may be common in pediatric idiopathic RP and pinpoint its severity: our exploratory study supports the routine assessment of vitamin D in children and adolescents with severe forms of RP, warranting prospective randomized controlled trials to determine whether correction of vitamin D deficiency may potentially improve disease severity. Full article

Marked interindividual variability in drug response remains a major challenge in clinical pharmacology and cannot be fully explained by host genetics alone. Increasing evidence indicates that the gut microbiota constitutes an additional determinant of drug efficacy and toxicity through bidirectional interactions with pharmacological therapies. This recognition has led to the emergence of pharmacomicrobiomics, a field that investigates how microbial communities influence drug disposition and response, and how drugs, in turn, alter the microbiome. Microbiome-mediated effects on drug efficacy and toxicity have been described across several therapeutic areas, including oncology, multiple sclerosis, and type 2 diabetes mellitus. Although these findings are promising, most mechanistic evidence derives from preclinical and animal studies, with relatively limited validation in controlled clinical trials. Strategies to modulate the gut microbiota, including prebiotics, probiotics, and faecal microbiota transplantation, have shown preliminary promise in optimising drug efficacy and reducing adverse effects, although methodological heterogeneity and incomplete mechanistic understanding limit their current clinical application. The identification of robust microbiome-derived biomarkers and the integration of multi-omics approaches, particularly metabolomics, are expected to accelerate the translation of pharmacomicrobiomics into precision medicine. This review summarises current evidence regarding microbiome–drug interactions, the mechanisms underlying microbiome-mediated modulation of pharmacokinetics and pharmacodynamics, emerging therapeutic strategies, and the challenges that remain before pharmacomicrobiomics can be implemented in clinical practice. Full article

Background/Objectives: Fruit, vegetable and berry (FVB) juice powder concentrates are increasingly used to support cardiovascular health. Since they are usually consumed over long periods, this study assessed the metabolic safety of a commercial FVB supplement and its impact on selected biomarkers of systemic oxidative stress and cardiovascular health. Methods: In this open-label, randomized controlled trial, generally healthy older adults were allocated to a control group (n = 16) or an FVB group (n = 18), ingesting six capsules/day. This work reports the pre-specified 6-month timepoint of a 1-year trial. The primary outcome, metabolic safety, was assessed by hepatic, renal, thyroid, lipid and glucose metabolism markers. Exploratory analysis assessed carbonyl proteins, malondialdehyde, and oxidized LDL as markers of systemic oxidative stress, together with homocysteine and blood pressure as markers of cardiovascular health, while plasma vitamin C served as a compliance marker. Results: The FVB concentrate was well tolerated, and no safety-relevant deteriorations were observed in the FVB group. Carbonyl proteins decreased significantly in the FVB group (interaction p = 0.030). Homocysteine remained stable in the FVB group but increased significantly in the control group (interaction p = 0.002). Furthermore, systolic blood pressure decreased significantly (interaction p = 0.036), with a comparable interaction of diastolic blood pressure (p = 0.011), and plasma vitamin C increased significantly in the FVB group (interaction p = 0.004). After adjustment for baseline values, age and BMI, between-group differences persisted for homocysteine and diastolic blood pressure, whereas the differences in systolic blood pressure and carbonyl proteins were attenuated and no longer reached statistical significance. Conclusions: Six months of supplementation with a commercial FVB concentrate was metabolically safe and well tolerated. Since these findings are based on a pre-specified timepoint and a limited number of participants, they are hypothesis-generating rather than confirmatory and require confirmation by the complete trial. Registered at ClinicalTrials.gov (NCT04763291; registered on 21 February 2021). Full article

Background/Objectives: OrganoHIPEC is a phase-II, two-stage, open-label clinical trial that investigates if cytoreductive surgery (CRS) and patient-tailored HIPEC, based on a preclinical platform using patient-derived organoids, can improve disease control in peritoneal metastases from colorectal cancer (CRC-PM). Methods: Adults with limited CRC-PM and no distant metastases were included. CRC-PM were sampled for organoid development during diagnostic laparoscopy. These organoids were used in an in vitro HIPEC model to test various drugs suitable for intraperitoneal administration. After 3–6 months of systemic chemotherapy, patients without progression underwent CRS/HIPEC with personalized regimens based on organoid drug response. To detect an increase in 12-month peritoneal disease-free survival from 40% to 60%, 24 patients are needed. According to the two-stage design, if <7 of 10 patients in Stage-1 remain PM-free at 12 months, the trial is terminated. Results: Forty-seven patients were enrolled. Among 31 patients with available organoid data, the most active drugs were mitomycin-C (n = 14), cisplatin/mitomycin-C (n = 12), and low-dose (120 min) oxaliplatin (n = 4). No patient was sensitive to high-dose oxaliplatin (30 min) and cisplatin/doxorubicin. Ten patients had a potential follow-up >12 months. Peritoneal relapse occurred at 8 months in two patients, and one died of liver metastases at 7 months. Seven patients remained PM-free for >12 months (median 16.4, range 12.6–28.4). Conclusions: A comprehensive precision approach using patient-derived organoids to guide personalized HIPEC is feasible and shows promising early results. High-dose oxaliplatin is poorly active. As 7/10 patients achieved the endpoint of 12-month PM-free survival, Stage-1 was successfully completed. The trial is proceeding to Stage-2. Full article

Panic disorder is a highly prevalent and impairing diagnosis in veterans. Despite consistent efficacy findings in community samples, few studies have investigated evidence-based psychotherapies in veterans with panic disorder, limiting the understanding of their utility and deployment in Veterans Affairs (VA) settings. The present study preliminarily investigated cognitive behavioral therapy (CBT) for panic disorder via a non-controlled design in a treatment-seeking veteran sample with panic disorder at the VA. Of the 41 veterans initiating treatment, 28 (68.3%) participants completed at least eight sessions of psychotherapy. In general, participants evidenced medium-to-large post-treatment effects across disorder-specific symptoms (panic and anxiety symptomatology), comorbid presentations (symptoms of depression and posttraumatic stress disorder), and overall functioning. Disorder-specific symptom effects remained stable for six months after psychotherapy was terminated. In addition, the delivery of CBT for panic disorder was further supported by positive indices of treatment feasibility, including treatment engagement, homework completion and engagement, and high participant satisfaction ratings. While recognizing that this study did not include a control group, the findings provide limited support for CBT treatment of panic disorder in veterans’ settings, findings that will require confirmation in a multisite controlled clinical trial. Full article

Background: Pain is a multidimensional experience shaped not only by nociceptive input but also by cognitive, emotional, and social processes. In musculoskeletal (MSK) rehabilitation, outcome variability among patients with similar clinical presentations suggests that determinants beyond tissue pathology may influence pain perception and recovery. Contextual factors (CFs)—communication, therapeutic relationship, patient expectations, and environmental cues—are increasingly recognized yet remain inconsistently integrated into routine practice. Objective: To map how CFs are represented in the physiotherapy literature indexed under that terminology, and to identify where empirical evidence in MSK rehabilitation is present and where it is absent. Methods: A narrative review with a systematic search strategy, reported following SANRA, was conducted in PubMed and Scopus, searched on 31 March 2026. Records were screened against predefined eligibility criteria, including publication from 2006 onwards and English language. Two reviewers independently screened records and resolved disagreements by consensus. Methodological quality was appraised using the Cochrane RoB2 tool for randomized controlled trials and an adapted Newcastle–Ottawa Scale for observational and cross-sectional studies. Conceptual publications were not formally appraised. Each publication was classified as direct clinical evidence (Tier A), indirect mechanistic or implementation-level evidence (Tier B), or conceptual contribution (Tier C). Results: Eight publications were included: no source provided direct clinical evidence in a musculoskeletal rehabilitation population (Tier A), five provided indirect mechanistic or implementation-level evidence (Tier B), and three were conceptual contributions (Tier C). The single randomised controlled trial retrieved was conducted in asymptomatic volunteers and was at high risk of bias for the between-group comparisons of all reported outcomes. Findings are organised as contextual domains, mediating mechanisms, and outcomes. No direct clinical evidence was retrieved; claims regarding expectations, therapeutic alliance, non-verbal communication, and the clinical environment rest on indirect or conceptual sources. Conclusions: CFs may contribute to pain and rehabilitation variability through cognitive, emotional, and relational pathways, complementing rather than replacing evidence-based care. The scarcity of direct clinical evidence within the literature indexed under this terminology is itself a finding. Construct-level searches and pragmatic trials are required to clarify the contribution of individual contextual domains. Full article

Background and Objectives: Sarcopenia and frailty are associated with falls, disability, and functional decline in older adults. This review evaluated traditional Chinese mind–body exercise (TCMBE), including Tai Chi and Health Qigong, in adults aged 60 years or older with clinically defined sarcopenia or frailty. Materials and Methods: Randomized controlled trials identified through December 2024 from six English- and Chinese-language databases were synthesized. The analyses included physical performance and secondary outcomes and explored sarcopenia and frailty as study-level subgroups. Results: Twenty-two trials involving 1660 participants were included. TCMBE was associated with a shorter Timed Up and Go Test time (mean difference [MD], −1.17 s; 95% CI, −1.80 to −0.54; p < 0.01; I² = 74%), a higher Short Physical Performance Battery score (MD, 0.99 points; 95% CI, 0.58 to 1.40; p < 0.01; I² = 24%), and greater grip strength (MD, 2.02 kg; 95% CI, 0.58 to 3.47; p = 0.006; I² = 89%). The 6 min walk test estimate was borderline and imprecise (MD, 11.76 m; 95% CI, 0.10 to 23.43; p = 0.05; I² = 0%), and no clear overall effects were observed for gait speed, the 30 s chair stand test, sit-to-stand time, Berg Balance Scale score, muscle mass, depressive symptoms, or quality of life. Several analyses showed substantial heterogeneity, and some subgroup estimates were based on only one or two studies. Conclusions: Low-certainty evidence suggests that TCMBE may produce small improvements in TUGT performance, SPPB scores, and grip strength. Very-low-certainty evidence leaves its effects on gait speed and quality of life uncertain. Risk-of-bias concerns, heterogeneity, imprecision, and uncertain clinical significance limit confidence in the current estimates. The available evidence is insufficient to support routine implementation, and larger, rigorously conducted randomized controlled trials are needed. Full article

Dental caries is a biofilm-mediated, non-communicable, multifactorial disease in which the balance between demineralization and remineralization determines whether an initial enamel lesion remains stable, arrests, or progresses toward cavitation. Contemporary caries management prioritizes preservation of tooth structure and emphasizes individualized decisions based on lesion activity, cavitation status, cleansability, radiographic depth, and patient’s caries risk. Resin infiltration has emerged as a microinvasive approach positioned between noninvasive preventive strategies and conventional restorative treatment. This evidence-based narrative review summarizes the current literature on resin infiltration for incipient, non-cavitated proximal carious lesions in permanent teeth, with emphasis on diagnosis, case selection, clinical protocol, and current evidence. A structured search of three databases (PubMed, Embase, and the Cochrane Central Register of Controlled Trials) identified randomized clinical trials, observational clinical studies, systematic reviews, narrative reviews, and relevant in vitro investigations. The strongest clinical evidence supports resin infiltration for non-cavitated proximal lesions in permanent teeth, particularly enamel and selected outer dentin lesions, where long-term studies demonstrate reduced radiographic progression. In vitro studies indicate that lesion penetration, enamel hardness, and surface roughness depend on lesion characteristics, pretreatment, and technique, and help explain the caries-arresting effect. Current evidence shows that resin infiltration should be considered a selective microinvasive option for incipient proximal caries, guided by lesion assessment and patient’s caries risk rather than a universal substitute for prevention or restoration. Full article

Background: Subjective cognitive complaints (SCCs) are common in middle-aged and older adults and may reflect early cognitive changes, alongside alterations in stress, mood, sleep, and quality of life. N-PEP-12 is a peptide-based nutritional supplement with potential neuroprotective effects, but evidence of its benefits in healthy adults with SCCs remains limited. Objective: To evaluate the effects of N-PEP-12 supplementation on attention, cognitive function, and mental wellbeing in healthy middle-aged and older adults with SCCs. Methods: In this prospective, randomized, double-blind, placebo-controlled trial, 276 participants aged 50–75 years with SCCs and no clinically significant cognitive impairment were randomized to placebo, N-PEP-12 45 mg, or N-PEP-12 90 mg. Assessments were performed at baseline and after 30, 90, and 180 days. Primary outcomes included Test of Attentional Performance measures. Secondary outcomes included WAIS-IV Digit Span Forward and Backward, perceived stress, mood, sleep quality, and EQ-5D-5L visual analog scale. Results: Across the three primary attention outcomes analyzed jointly in a multivariate repeated-measures model, there was a significant group-by-visit interaction (p = 0.003) and a significant effect of visit (p < 0.001), without a significant main effect of treatment arm (p = 0.133), indicating a time-dependent treatment effect. This result was obtained in a sensitivity analysis population in which missing values were imputed under assumptions least favorable to the active arms. In exploratory endpoint-specific comparisons at 90 days, both N-PEP-12 groups showed greater improvements than placebo in alertness, attention omissions and memory omissions, and Digit Span Forward and Backward scores also improved. In a subsequent uncontrolled extension phase, in which all participants received active treatment, participants initially assigned to placebo showed comparable improvements after switching to N-PEP-12 90 mg. These observations are exploratory. Adverse events were infrequent and similarly distributed across groups. Conclusions: N-PEP-12 supplementation was associated with improvements in attention, working memory, and mental wellbeing in healthy middle-aged and older adults with subjective cognitive complaints. These findings support further investigation of N-PEP-12 as a nutritional intervention for early subjective cognitive changes associated with aging. Full article