Search Results (639)

Persistent postoperative opioid use (PPOU) is an emerging challenge in pediatric perioperative care, with rates as high as 4.7% in opioid-naive adolescents. Despite advances in multimodal analgesia, current protocols often fail to prevent long-term opioid exposure, particularly after high-risk surgeries such as spinal fusions. While multiple strategies exist to reduce PPOU in children, including regional anesthesia and non-opioid analgesics, this review specifically focuses on methadone and pharmacogenomic-guided opioid prescribing as promising approaches. Methadone, a long-acting opioid with mu-opioid agonism, NMDA antagonism, and monoamine reuptake inhibition, has shown encouraging outcomes in adult and emerging pediatric studies but remains underutilized due to concerns over safety, variability, and familiarity. This narrative review explores the intersection of methadone pharmacology, pharmacogenomic (PGx)-guided opioid prescribing, and their potential to reduce PPOU and optimize perioperative pain control in children. We examine methadone’s unique pharmacokinetic profile, extended half-life, and ability to reduce central sensitization and opioid tolerance. Data from pediatric trials in cardiac, spinal, and major abdominal surgeries are reviewed, highlighting methadone’s potential to lower total opioid use, stabilize postoperative pain trajectories, and improve recovery. The review also discusses the role of PGx testing, particularly CYP2D6, CYP3A4, UGT2B7, and OPRM1 variants, in tailoring methadone dosing to individual metabolic profiles, reducing adverse effects, and improving analgesic efficacy. There are no well accepted generalizable perioperative methadone dose, number of doses and dosing intervals due to limited large multicenter studies in children. We outline challenges, including QTc prolongation, dosing variability, lack of pediatric-specific PGx guidelines, and ethical considerations around genetic testing in minors. The review calls for multidisciplinary perioperative teams, expanded PGx implementation, and real-world data from registries and AI-integrated models to support precision opioid strategies. Preventing PPOU in children is critical. Integration of methadone-based multimodal analgesia in high-risk painful in-patient procedures and future integration of PGx represent positive steps toward personalized, effective, and safer pain management in pediatric surgical patients, an urgent need as opioid stewardship becomes a clinical and public health imperative. Full article

Urban green spaces are pivotal to enhancing carbon sinks and advancing carbon neutrality goals, yet the structural complexity of green space units often leads to scale mismatches and weak spatial responsiveness in current assessments. This study develops an integrated evaluation framework that combines landscape spatial unit typologies with life-cycle-based carbon flux modeling. We defined 22 landscape spatial unit types based on two-dimensional surface cover and three-dimensional vegetation structure, including waterbodies and vertical greening. A life-cycle carbon model was developed with indicators covering unit carbon sink, unit carbon emission, unit net carbon sink efficiency, and time to carbon balance. Taking Luhe Park in Nanjing as a case study, the carbon sink efficiency indicators were quantified for 108 units over a 50-year cycle. Results indicate that multilayer vegetation structures, high green coverage, and moderate-to-high planting density markedly enhance carbon sink efficiency, whereas extensive built surfaces and high impervious ratios suppress it. K-means clustering classified the spatial units into four types with emphasis on efficiency-driven, structural optimization, functional compatibility, and imbalance compensation, respectively, revealing a clear gradient tied to spatial configuration. To translate diagnosis into design, we report 95% confidence intervals of key structural factors as actionable thresholds. These ranges inform targeted interventions such as maintaining continuity and multilayer structure in high-efficiency areas, modest structural upgrades with native drought-tolerant plants, edge greening with permeable pavements in open spaces, and streamlined vertical systems linked to adjacent high-sink ground units. The framework delivers spatially explicit, life-cycle-aware evidence to support low-carbon planning and design of urban green spaces. Full article

Background: Acne vulgaris is a common inflammatory disorder with significant clinical and psychosocial impacts. Medium-depth chemical peels are increasingly used to manage both active acne lesions and atrophic acne scars. This study aimed to quantitatively assess the clinical effectiveness of a novel multimodal medium-depth chemical peel regimen, yellow peel, in improving acne severity and scar depth, as well as skin hydration and sebum production in patients with mild to moderate facial acne. Methods: Twenty patients (17 women and 3 men) aged 20–25 with mild to moderate acne vulgaris underwent two sessions of yellow peel treatment at four-week intervals. The peel protocol combined glycolic acid, salicylic acid, and a multi-acid mask containing retinol, azelaic, phytic, kojic, and salicylic acids. Clinical outcomes were evaluated at baseline, four weeks after the first peel, and two months after the second peel. Assessments included the Investigators Global Assessment (IGA), inflammatory lesion count, 3D scar depth analysis, skin hydration (corneometer), and sebum secretion (sebumeter). Results: Yellow peel treatment significantly reduced acne severity, with an 85% decrease in inflammatory lesion counts and over 20% reduction in scar depth. Skin hydration improved significantly across all facial regions, and sebum secretion decreased substantially, enhancing skin barrier function and seboregulation. Statistical analysis confirmed the treatment’s efficacy with sustained improvements two months post-final peel. Conclusions: The yellow peel protocol is an effective and well-tolerated adjunct therapy for managing mild to moderate acne and atrophic acne scars. By combining exfoliative, anti-inflammatory, antibacterial, sebostatic, and depigmenting agents, this multimodal approach delivers comprehensive skin improvement. Further large-scale, controlled studies are recommended to confirm long-term safety and efficacy. Full article

Background and Objectives: Acne vulgaris is a prevalent chronic inflammatory skin condition affecting adolescents and young adults worldwide. Increasing concern regarding antimicrobial resistance has renewed interest in microbiome-modulating therapies, including oral probiotics. This systematic review and meta-analysis evaluated the efficacy and safety of oral probiotic supplementation for acne vulgaris using contemporary random-effects methods. Materials and Methods: Following PRISMA 2020 guidelines, we searched PubMed, Embase, Web of Science, and ClinicalTrials.gov through November 2025 without language restrictions. Eligible studies were double-blind randomized controlled trials (RCTs) comparing oral probiotics with placebo or standard therapy for ≥4 weeks and reporting quantitative acne severity outcomes. Risk of bias was assessed using RoB 2.0. Standardized mean differences (SMDs) were pooled using restricted maximum likelihood (REML) with Hartung–Knapp adjustment. Heterogeneity was summarized using I², τ² (95% CI), and 95% prediction intervals. Adverse events were extracted. Results: Three RCTs (n = 231) met eligibility criteria. Pooled analysis suggested a modest reduction in inflammatory lesion counts favoring probiotics (SMD −0.57; 95% CI −0.94 to −0.21), although heterogeneity was substantial (I² = 72%; τ² = 0.11). The 95% prediction interval (−1.25 to 0.11) indicated that future studies may plausibly observe no meaningful effect. Sensitivity analyses using the DerSimonian–Laird estimator produced comparable results. All trials reported good short-term tolerability with no serious adverse events. Risk of bias was low in two trials and of some concern in one. Certainty of evidence was rated low to moderate. Conclusions: Oral probiotics may modestly reduce acne severity as a generally safe, antibiotic-sparing adjunct; however, the current evidence base is small and heterogeneous, and the certainty of effect remains low-to-moderate. Larger, standardized RCTs are required before firm clinical recommendations can be made. Registration: PROSPERO CRD420251181388. Funding: This research received no external funding. Full article

Background and aims: This study aimed to determine whether neuromuscular electrical stimulation (NMES) combined with nutritional counseling promotes an increase in thigh muscle thickness (MT), as well as to assess changes in the relationship between MT and intracellular water (ICW). Body composition methods such as ultrasound may overestimate muscle mass, depending on the context, because they cannot distinguish the contractile protein component from body fluids, including intra- and extracellular water. Methods: A pilot randomized parallel trial was conducted with 25 hospitalized patients with unselected cancer, who were divided into two groups: NMES + Diet and Diet. Both groups received nutritional counseling, but only one group received NMES. NMES was applied bilaterally to the origin and insertion points of the quadriceps twice daily, with a 3 h interval between sessions, for 7 consecutive days. MT and ICW were measured before and after the intervention. Food consumption was assessed using a 24 h dietary recall at baseline and at the end of the study to quantify and adjust macronutrient intake during the intervention. Results: Both treatment groups (Diet × NMES + Diet) showed similar dropout rates which means participants in the more intensive treatment did not quit more frequently, once intervention with NMES was feasible and well tolerated. In addition, both groups showed a reduction in carbohydrate intake (p = 0.012) and an increase in leucine intake (p < 0.001) post-intervention. The increase in leucine intake was significantly greater in the NMES + Diet group (p < 0.001), and the reduction in carbohydrate intake was also greater in this group (p = 0.012). In the delta analysis, the NMES + Diet group showed an increase in thigh MT, whereas the Diet group experienced a decrease (Diet group: ∆ = −2.53 ± 3.73 mm vs. NMES + Diet group: ∆ = 2.09 ± 2.27 mm, p = 0.001). Moreover, the MT/ICW ratio was higher in the NMES + Diet group post-intervention (Diet group: ∆ = −0.15 ± 0.19 mm/L vs. NMES + Diet group: ∆ = 0.11 ± 0.09 mm/L, p < 0.001), while no significant difference in ICW was observed between groups. Conclusions: short-term intervention combining nutritional counseling with NMES increased thigh MT and the MT/ICW ratio, possibly due to NMES-induced extracellular water expansion. Full article

Background/Objective: Type 2 diabetes mellitus (T2DM) is a known risk factor for cardiovascular disease (CVD); however, not all individuals with T2DM have the same CVD risk. Traditional glycemic cluster analyses of individuals with diabetes using the homeostatic model assessment estimate of insulin resistance (HOMA-R) as an indicator of insulin resistance have identified severe insulin-resistant diabetes as a high-risk factor for incident CVD. To extend this observation, we further classified non-diabetic individuals to identify risk clusters for incident CVD. Methods: We performed hierarchical cluster analysis of 577 non-diabetic Japanese individuals using the glycated hemoglobin level, body mass index, homeostasis model assessment estimate of β-cell function, and the triglyceride-glucose (TyG) index instead of the HOMA-R to assess incident CVD risk over up to 188 months. Results: Analysis using a multiple risk factor-adjusted Cox proportional-hazard regression model showed that in addition to impaired glucose tolerance (IGT), among the four clusters observed, a cluster labeled “low insulin secretion (Low-IS (TyG))” was a risk factor for incident CVD (hazard ratio, [95% confidence interval]: 2.77 [1.11–6.91]). Furthermore, when the participants were stratified on the basis of the presence of IGT, the Low-IS (TyG) cluster was associated with an increased risk of CVD only in the non-IGT group (3.29 [1.32–8.18]), but not in the IGT group (1.66 [0.34–8.15]). Conclusions: Glycemic clustering incorporating the TyG index identified a novel at-risk group for incident CVD among non-diabetic individuals, offering a useful tool for early CVD risk stratification beyond traditional measures of glucose tolerance. Full article

Thepaper presents an efficient model predictive control framework formulated as a linear programming problem to control a servo drive with model uncertainty considerations from the viewpoint of the control performance. The model predictive framework is used to adopt $L_1$-type cost functions using absolute tracking errors, providing computational efficiency and enabling real-time implementation. A key contribution is the deployment of this approach on real hardware in a hardware-in-the-loop setting, supported by fully open-source code for Simulink Coder and C environments, verifying the solution scheme in real time. Experimental validation on a servo drive demonstrates the system’s tolerance for parameter uncertainties with slight performance degradation, resulting in an up to 18% increase in the considered control quality measure, between nominal parameters’ values and the worst configuration. The proposed linear programming approach enables constraint handling imposed on control signals and supports the arbitrary choice of prediction horizons and sampling intervals. The paper also includes a comprehensive derivation of the control law, controller implementation details, and stepwise experimental results showcasing the impact of uncertainties on control performance. This work and the attached code enable the authors to easily reproduce the proposed approach and extend it in their applications. Full article

Drought stress, intensified by climate change, poses a significant threat to global rice security. To identify stable quantitative trait loci (QTL) associated with drought tolerance in rice under different genetic backgrounds and environmental conditions, this study combined 901 drought-tolerant QTLs reported in 52 independent studies published between 2000 and 2023, which were subsequently meta-analyzed and condensed into 77 meta-QTLs (MQTLs). Among them, 23 MQTLs were validated in seven independent genome-wide association studies (GWAS) on drought tolerance in rice, each conducted using different natural populations. The confidence intervals (CIs) of the MQTLs were substantially narrowed, with the reduction factor ranging from 2.44 to 20.40 relative to the original QTLs. To further explore key genes for drought tolerance, we screened for genes located within the MQTL regions and differentially expressed in our RNA-seq data, yielding 3851 drought-responsive differentially expressed genes (DEGs). These DEGs were then subjected to a refinement process that included Mfuzz clustering, cis-regulatory element (CRE) analysis, protein–protein interaction (PPI) network analysis and AlphaFold-based structural modeling of their encoded proteins. This stepwise filtering identified eleven drought-responsive hub proteins, nine with annotated functions and two functionally uncharacterized. Following further prioritization, LOC_Os04g35340 and Os07g0141400 were established as core candidate genes (CGs) for dissecting the genetic and biochemical basis of drought tolerance in rice. Full article

Objectives: We examined how opposing running slopes can modulate interval training effects on aerobic performance and reduction–oxidation (REDOX) determinants. Methods: Fourteen physically active volunteers, assigned to either the Uphill group (UG) or the Downhill group (DG), completed 16 workouts of ten 30-s runs, at either +10% or −10% grade, with a work-to-rest ratio of 1:2 at 90% of their Maximum Aerobic Speed (MAS) over 8 weeks. Maximal oxygen uptake (VO_2max), MAS, Running Economy (RE), time to exhaustion at MAS (Tmax), respiratory exchange ratio (RER), and blood lactate at rest, 5th, and 10th runs were evaluated pre-, mid-, and post-training. Also, REDOX markers [Total Antioxidant Capacity (TAC), Protein Carbonyls (PCs) were assessed in blood samples taken at rest and 3 min post-exercise of the first and last workouts. Results: VO_2max was unchanged in both groups; in the DG, MAS increased (from 14.2 ± 1.7 to 15.0 ± 1.5 km/h, d = 0.43), and post-training RER significantly increased (from 1.06 ± 0.07 to 1.12 ± 0.03). In the last training session, blood lactate levels increased in the UG (from 9.30 ± 2.69 mmοl/L to 13.34 ± 4.64 mmοl/L) but remained low and unchanged in DG (<2 mmοl/L). Post-training, resting TAC decreased in both groups, and the exercise-induced rise in PC levels was attenuated. Conclusions: Despite the brief intervention, VO₂max levels were maintained in both groups, with divergent changes in metabolic, REDOX, and performance indicators; uphill HIIT may serve for enhancing lactate tolerance, while downhill intermittent running may improve running economy. Full article

Introduction: Suppressive antibiotic therapy (SAT) is a therapeutic alternative for complex infections where a cure is considered unlikely or impossible. SAT involves the prolonged, often indefinite, administration of antibiotics, typically given orally, to control symptoms. However, the increasing incidence of multidrug-resistant microorganisms limits the availability of oral options. Dalbavancin is a parenteral antibiotic with broad coverage against Gram-positive bacteria that offers the advantage of an extended dosing interval. The aim of this study was to describe the characteristics and clinical outcomes of patients with implant-associated osteoarticular infections receiving dalbavancin as SAT. A secondary objective was to identify factors associated with SAT failure with dalbavancin. Materials and Methods: We conducted a multicentre, observational study with retrospective recruitment of patients treated with dalbavancin as (SAT) for complex implant-associated osteoarticular infections, in which curative surgery was either not feasible or insufficient. Cohort characteristics were described, and variables associated with SAT failure under dalbavancin treatment were analysed. Results: A total of 43 patients received dalbavancin as SAT. The most frequent indication was prosthetic joint infection (38 [88.4%]). A total of 28 patients (65.1%) had chronic infections; the remaining cases were acute infections that had failed conservative management. Nine different dosing regimens of dalbavancin were used. Dalbavancin provided adequate symptomatic control in 32 patients (74.4%) over a follow-up period of 836.5 days (IQR 402–1288.5). The antibiotic was well tolerated; only one adverse effect was reported in a patient. Three patients developed resistance during treatment, which accounted for SAT failure. Conclusions: Dalbavancin is shown to be a safe and convenient alternative for SAT for orthopaedic implant infection. Although the development of resistance was infrequent, it can occur and should be monitored. Full article

Background: Coronary artery disease remains the leading cause of morbidity and mortality in developed countries. Despite advances in treatment and standard rehabilitation, conventional programs may be monotonous and insufficiently engaging. Normobaric hypoxia, simulating high-altitude conditions, has emerged as a potential method to enhance cardiovascular adaptations in post-myocardial infarction (MI) patients. Objective: This study aimed to compare the efficacy and safety of exercise-based cardiac rehabilitation performed under normobaric hypoxia corresponding to altitudes of 2000 m and 3000 m above sea level in patients after MI treated with percutaneous coronary intervention (PCI). Methods: A total of 61 male post-MI patients (mean age 60.4 ± 8.9 years) were randomized into two groups: training under simulated altitudes of 2000 m (n = 35) or 3000 m (n = 26). The 22-day program consisted of interval ergometer sessions. Pre- and post-intervention assessments included cardiopulmonary exercise testing (CPET), echocardiography, and tissue Doppler imaging (TDI). Results: Both groups demonstrated significant improvements in exercise tolerance. Training at 2000 m significantly increased test duration (r = 0.735) and peak heart rate (r = 0.467). At 3000 m, additional benefits were observed, including improvements in metabolic equivalent (r = 0.861), peak oxygen consumption (d = 0.81), and reduction in respiratory exchange ratio (r = 0.682). Intergroup analysis revealed moderate differences favoring the 3000 m group in MET, breathing frequency, and RER. Echocardiography showed beneficial remodeling in both groups, with improvements in LV dimensions, ejection fraction, and MAPSE. Notably, training at 2000 m resulted in more consistent echocardiographic benefits compared to 3000 m. Conclusions: Cardiac rehabilitation under normobaric hypoxia is effective and safe in stable post-MI patients. Training at 3000 m provides greater improvements in exercise tolerance, while 2000 m confers more favorable effects on cardiac structure and function. These findings suggest that moderate hypoxic exposure (2000 m) may represent an optimal balance between efficacy and safety in post-MI rehabilitation. Full article

To address the economic and reliability challenges of high-penetration renewable energy integration in electricity-heat-hydrogen integrated energy systems and support the dual-carbon strategy, this paper proposes an optimal dispatch method integrating Information Gap Decision Theory (IGDT) and Fuzzy Chance-Constrained Programming (FCCP). An IES model coupling multiple energy components was constructed to exploit multi-energy complementarity. A stepped carbon trading mechanism was introduced to quantify emission costs. For interval uncertainties in renewable generation, IGDT-based robust and opportunistic dispatch models were established; for fuzzy load uncertainties, FCCP transformed them into deterministic equivalents, forming a dual-layer “IGDT-FCCP” uncertainty handling framework. Simulation using CPLEX demonstrated that the proposed model dynamically adjusts uncertainty tolerance and confidence levels, effectively balancing economy, robustness, and low-carbon performance under complex uncertainties: reducing total costs by 12.7%, cutting carbon emissions by 28.1%, and lowering renewable curtailment to 1.8%. This study provides an advanced decision-making paradigm for low-carbon resilient IES. Full article

Background: Lowering lipid levels after an acute coronary syndrome is critical for preventing recurrent adverse cardiovascular events. Multiple medications are now available, but there is limited evidence comparing how frequently they lead to the achievement of guideline-recommended lipid targets. Methods and Results: This observational study evaluated the impact of novel lipid-lowering therapies (alirocumab, evolocumab, inclisiran, and bempedoic acid) in patients with a history of atherosclerotic cardiovascular disease or familial hypercholesterolaemia treated with maximum-tolerated doses of high-intensity statin therapy with or without ezetimibe. Our primary assessment was the achievement of LDL-C below 1.4 mmol/L as per the European Society of Cardiology guidelines. The study comprised of 256 patients. Reduction in LDL-C was greatest with alirocumab and evolocumab, achieving a reduction of 62% (95% confidence interval [CI], 51 to 93; p < 0.001) and 58% (95% CI, 47 to 88; p < 0.001) after 12 months, respectively. This was followed by inclisiran with a reduction of 47% (95% CI, 37 to 78; p < 0.001) and bempedoic acid with a reduction of 36% (95% CI, 22 to 69; p < 0.001). Patients treated with alirocumab and evolocumab started from a higher baseline LDL-C than inclisiran, due to the higher LDL threshold required for initiation of alirocumab and evolocumab in the UK. Despite this, inclisiran, evolocumab, and alirocumab were all associated with similar proportions of patients achieving LDL targets: 35%, 42%, and 37% of patients achieved a guideline-recommended LDL-C target of <1.4 mmol/L. Patients with a baseline LDL-C > 4 mmol/L were more likely to reach the ESC target when treated with alirocumab or evolocumab compared to inclisiran, with results of 33.3% vs. 24.1% (p = 0.016) and 35.7% vs. 24.1% (p = 0.05). Conclusions: Alirocumab and evolocumab were associated with the greatest reductions in LDL-C, followed by inclisiran and bempedoic acid. Overall, alirocumab, evolocumab, and inclisiran led to approximately 40% of patients reaching ESC targets for LDL-C. In patients with a baseline LDL-C > 4 mmol/L, significantly more patients achieved LDL-C targets when treated with alirocumab or evolocumab compared to inclisiran. Strength and limitations: This was the first study to comprehensively compare the efficacy of novel lipid-lowering therapies in achieving guideline-recommended LDL targets within a high-risk cardiovascular population. The sample size was relatively small, especially for patients treated with bempedoic acid. Full article

Freshwater scarcity and saline groundwater are major constraints for maintaining green roofs in coastal areas. This study evaluated the response of Jacobaea maritima subsp. sicula, (Sicilian silver ragwort) a drought-tolerant coastal ornamental plant, to tap water and seawater irrigation under Mediterranean summer conditions. Plants were grown in 10 cm-deep green-roof modules and subjected to six irrigation regimes: tap water, seawater, or alternating tap water and seawater, each applied at 4- or 8-day intervals, with irrigation volumes equal to 60% of cumulative reference evapotranspiration (ET_o). Growth, relative water content (RWC), chlorophyll index (SPAD), and leachate electrical conductivity were monitored to assess plant performance and salinity responses. Seawater irrigation caused rapid substrate salinization, leaf dehydration, and plant death within one month, while alternating seawater with tap water also failed to sustain survival. In contrast, tap water–irrigated plants maintained high RWC, chlorophyll content, and stable visual quality throughout the experimental period, even with deficit irrigation at 60% ET_o every eight days. These findings demonstrate that J. maritima subsp. sicula is well suited for freshwater-irrigated extensive green roofs in semi-arid regions, providing reliable performance under infrequent irrigation and limited water supply. However, seawater or high-salinity irrigation should be avoided. Future research should explore mixed freshwater–seawater irrigation regimes with a higher freshwater proportion, aiming to reduce total freshwater consumption while sustaining plant survival and esthetic performance. Full article

This paper addresses the cooperative formation control problem for a heterogeneous unmanned system composed of Unmanned Surface Vehicles (USVs) and Autonomous Underwater Vehicles (AUVs) under coexisting constraints of actuator faults, time-varying communication topology, and communication delay. First, a unified dynamic model is established under the Euler–Lagrange framework. Building on this, a novel distributed adaptive fault-tolerant control (DAFTC) framework is proposed. This framework integrates a Dynamic Event-Triggered Mechanism (DETM) to address communication bandwidth limitations, alongside an adaptive fault-tolerant strategy to enhance system robustness. The novelty lies in the cohesive integration of DETM for communication efficiency and adaptive laws for online fault compensation (both loss of effectiveness and bias), while rigorously handling communication delays via Lyapunov–Krasovskii analysis. It is proven via Lyapunov stability analysis that the proposed control protocol ensures all signals in the closed-loop system remain semi-globally uniformly ultimately bounded, with the formation tracking error converging to an adjustable compact set. Simulation results demonstrate the framework’s effectiveness. Compared to periodic communication (0.1 s interval), the proposed DETM reduces the communication load by over 99.6%. Even when subjected to a 25% effectiveness fault and a 5 Nm bias fault, the root-mean-square (RMS) tracking error is maintained below 0.15 m, validating the system’s high performance and robustness. Full article