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Postoperative pain represents a significant challenge after breast surgery, emphasizing the need for effective perioperative pain management. Guided by enhanced recovery after surgery (ERAS) principles, multimodal analgesia strategies centered on nerve block have become a prominent clinical research focus. This review comprehensively explores the evolution of nerve block techniques in breast surgery, ranging from the "gold standard" thoracic paravertebral block (TPVB) to newer thoracic fascial plane blocks, including the pectoral nerve blocks (PECS), serratus anterior plane block (SAPB), erector spinae plane block (ESPB), and other innovative approaches. It evaluates the relative benefits and limitations of various techniques regarding analgesic efficacy, opioid-sparing potential, safety, and procedural simplicity. Beyond traditional acute pain management, this review addresses the prevention of chronic post-mastectomy pain syndrome (PMPS), improvements in postoperative recovery quality, and potential effects on oncological outcomes. This review emphasizes the importance of designing individualized precision nerve block strategies based on the surgical scope (e.g., breast-conserving surgery, mastectomy, axillary lymph node dissection, and breast reconstruction) and the distinct features of each technique. No single nerve block technique fits all scenarios; clinical decision-making should focus on selecting the most appropriate approach tailored to the specific patient and procedure. Future research should prioritize high-quality trials for emerging techniques, long-term outcome evaluations, and the development of standardized nerve block protocols to enhance evidence-based practices in this domain.

In this narrative review, we summarize the current state of knowledge on novel isoquinolinium chlorofumarate diesters and pinnatoxins as potential neuromuscular blocking agents for modern anesthesia. Isoquinolinium derivatives gantacurium, CW002, CW011, and CW1759-50 are discussed due to promising initial findings, with animal and human studies presented to assess which agent may have the greatest potential for future clinical use. The approval process for gantacurium has reached Phase III clinical trials, but further trials are no longer ongoing. CW002 has undergone animal and human testing, and early results suggest fewer cardiovascular and pulmonary adverse effects; however, CW002 produces a longer neuromuscular block and is more difficult to antagonize than gantacurium. CW011 and CW1759-50 have been tested only in animal models. We also describe agents used to reverse neuromuscular block. L-cysteine is an amino acid that reverses the described fumarate-based neuromuscular blocking agents by reacting with the carbon-carbon double bond to form a stable thioether adduct that cannot bind to acetylcholine receptors. This adduct then slowly hydrolyses into inactive fragments, enabling rapid and complete reversal. Calabadion binds aminosteroid and benzylisoquinoline neuromuscular blockers by forming "host-guest" complexes, rapidly binding free relaxant molecules in plasma and acting faster than sugammadex, making it a potentially promising reversal agent. This article aims to review the role of nondepolarizing neuromuscular blocking agents in anesthesia.

Random allocation is essential in randomized controlled trials (RCTs) to ensure impartial treatment allocation and minimize selection bias. Despite permuted block design (PBD) is used in approximately 75% of RCTs, it has long been criticized for its predictable allocation sequences-due to periodic rebalancing of group sizes-which compromises allocation concealment and undermines randomization integrity. Although numerous proposed alternatives, few have achieved widespread adoption. There remains a pressing need for a simple, intuitive, and universally applicable alternative to PBD that preserves its treatment balance and operational simplicity while dramatically improving allocation unpredictability. We propose a novel approach-Sandwich Mixed Randomization (SMR)-a conceptually simple and operationally feasible method that integrates complete randomization with PBD within a "sandwich" framework to enhance allocation unpredictability while preserving group size balance. Using Monte Carlo simulations of 1:1 two-arm open-label RCTs under strict allocation concealment (per Good Clinical Practice), we evaluated SMR across small (n = 48), medium (n = 240), and large (n = 1,200) trials. SMR was compared with fixed- and variable-sized PBD using the well-established metrics: treatment imbalance (absolute group size difference), allocation predictability (proportion of correct guesses), and a newly introduced metric-the relative excess risk of selection bias-benchmarked against the ideal performance of complete randomization. While PBD ensures perfect treatment balance, it exhibits high allocation predictability. Under pre-randomization guessing during enrollment, correct guess proportions reached 70.83% for fixed block size 4 and exceeded 68% for variable block sizes (4, 6, 8) and fixed size 6-far above the 50% benchmark of complete randomization. In contrast, SMR maintains balanced group sizes while reducing correct guess proportions to ~56% in small trials and ~53% in larger ones. Compared to variable-sized PBD, SMR reduces the risk of selection bias by >66% in small trials and >81% in larger ones. Across all sample sizes, the PBD-to-SMR risk ratio for selection bias consistently exceeds 3, underscoring the substantial bias risk associated with conventional PBD. The inherent predictability of PBD, regardless of fixed or variable block size, significantly increases the risk of selection bias, warranting caution in interpreting results from PBD-based trials. SMR substantially reduces this risk and offers a universally applicable, low-effort alternative to PBD across all RCT settings, including open-label, single-blinded, and multi-center designs. Its benefits remain meaningful even in double-blind RCTs with imperfect masking. Transitioning from conventional PBD to SMR enhances randomization integrity, strengthens internal validity, and reinforces the RCT as the gold standard for generating reliable, unbiased clinical evidence.

Neuromuscular blocking agents (NMBAs) are the leading cause of perioperative anaphylaxis. In confirmed cases with limited non-cross-reactive options, safe anesthesia requires coordination and muscle relaxant-free strategies. A 64-year-old woman with confirmed rocuronium-induced anaphylaxis and multiple comorbidities-including poorly controlled diabetes, coronary artery disease, chronic obstructive pulmonary disease, and obesity-underwent laparoscopic anterior resection of the sigmoid colon. General anesthesia was induced and maintained without muscle relaxants using total intravenous anesthesia and regional blocks. Airway topicalization and deep anesthesia enabled smooth intubation. Bilateral transversus abdominis plane and rectus sheath blocks provided effective somatic analgesia and abdominal relaxation. Ventilation and hemodynamic parameters remained stable throughout. The patient recovered uneventfully, without agitation or delayed arousal, and was discharged uneventfully on postoperative day 5. This report describes the feasibility of NMBA-free general anesthesia using intravenous agents and targeted regional blocks in high-risk patients with confirmed anaphylaxis, even in laparoscopic procedures.

The use of neuromuscular blocking agents (NMBAs) offers several advantages during surgery under general anesthesia because they help secure the surgical field and facilitate appropriate mechanical ventilation. Eliminating postoperative residual neuromuscular blockade (rNMB) remains a major challenge for anesthesiologists. Despite the use of intermediate-acting NMBAs and sugammadex, the incidence of rNMB still remains close to 50%. Although it is relatively easy to distinguish rNMB from a serious adverse reaction in healthy patients in the postanesthesia care unit, the effects of anesthesia make it much more difficult to rule out rNMB in critically ill patients. Although there were no comprehensive guidelines for NMBA management for decades, the most crucial step is now no longer the assessment of blockade depth based on subjective clinical tests or qualitative neuromuscular monitoring (NMM), but rather the appropriate use of NMBAs and reversal agents, and extubation guided by objective, quantitative monitoring. Accordingly, the American Society of Anesthesiologists, the European Society of Anaesthesiology and Intensive Care have published practical guidelines for preventing rNMB over the past five years, recommending appropriate use of NMBAs and reversal agents and the incorporation of quantitative NMM as standard monitoring whenever NMBAs are used. Furthermore, with recent advances in electromyography and the increasing availability of NMM, education on its proper use is essential.

Rotavirus (RV) is a major pathogen causing viral diarrhea in infants and various young animals, with Group A rotavirus (RVA) being the most prevalent. Porcine rotavirus A (PoRVA) causes severe gastroenteritis in piglets. VP6, a conserved immunogenic protein of PoRVA, serves as an ideal target for developing diagnostic assays and vaccines. Current indirect ELISAs for PoRVA antibody detection are prone to false positives, however, blocking ELISA (bELISA) offers superior specificity, hence the importance of developing VP6-targeting blocking mAbs. In this study, a highly expressing CHO-K1 cell line for VP6 was constructed, yielding VP6 with good immunogenicity. Subsequently, one mAb-3B3 with blocking activity was prepared using hybridoma technology. Molecular docking and molecular dynamics simulations determined that the binding between mAb-3B3 and VP6 is reliable and stable, and identified the conserved key interacting amino acids Tyr159, Thr367, and Val236, which provides a structural basis for the design of novel vaccines. Based on mAb-3B3, a bELISA method was first developed. ROC curve analysis (50 negative and 50 positive sera) determined a cutoff value of 23.23%, yielding an AUC of 0.9973 and 98.04% sensitivity and specificity. This bELISA can clearly distinguish between positive and negative serum. Moreover, the assay displayed no cross-reactivity with antisera against six common pig pathogens. This assay demonstrated 95.65% concordance with the indirect fluorescent antibody test among 186 clinical samples, validating its practical application. With high specificity, sensitivity, and reproducibility, this bELISA applies to clinical diagnosis of PoRVA and assessment of vaccine-induced immunity, aiding effective control of RVA.

Effective perioperative analgesia is essential to prevent abrupt changes in cerebral blood flow following carotid endarterectomy (CEA). We aimed to evaluate whether multimodal analgesia, including intermediate cervical plexus block (CPB), reduces 24 h postoperative opioid consumption compared with local infiltration. This randomized, observer-blinded study included 40 patients undergoing CEA. Patients were randomly allocated to either the multimodal group (multimodal analgesia with intermediate CPB, n = 20) or the control group (local infiltration, n = 20). The primary outcome was 24 h intravenous (IV) opioid conversion to IV morphine equivalents. Secondary outcomes included pain scores at rest and during motion, time to first opioid use, hypertension incidence, antihypertensive use, postoperative nausea/vomiting, satisfaction with pain management, quality of first-night sleep, Korean version of the Quality of Recovery-15 (QoR-15K) scores, complications, cerebral hyperperfusion syndrome, and intraoperative analgesia nociception index values. In the intention-to-treat analysis, 24 h postoperative opioid consumption was 13.3 (6.7, 20.0) mg and 10.0 (6.7, 13.3) mg in the control and multimodal groups, respectively, with no significant difference (P = 0.191). The multimodal group had significantly lower immediate postoperative pain at rest (P < 0.001) and during movement (P < 0.001), as well as longer time to first opioid use (P = 0.047) and higher QoR-15K scores (P = 0.004). No significant differences were observed in the other parameters. Multimodal analgesia with intermediate CPB did not reduce 24 h opioid consumption after CEA. However, it was associated with better early postoperative pain control and recovery scores.

The interaction between 2-amino-5-methylpyridinium and heavy p-block metal chlorides (Sn, Sb, and Bi) results in the formation of three hybrid compounds: (C6H9N2)2SnCl6, (C6H9N2)3[BiCl6], and (C6H9N2)2[Sb2Cl8]. Their structural, optical, and electrical properties were systematically examined by powder X-ray diffraction, UV-visible spectroscopy, and complex impedance spectroscopy in order to elucidate the effect of metal-center substitution on their physical behavior. Optical analysis reveals a gradual narrowing of the band gap from Sb- to Bi-containing compounds. The estimated band gap energies are 3.49 eV for (C6H9N2)2[Sb2Cl8], 3.36 eV for (C6H9N2)2SnCl6, and 3.10 eV for (C6H9N2)3[BiCl6], indicating enhanced electronic delocalization with increasing atomic number. Electrical measurements demonstrate a negative temperature coefficient of resistance (NTCR) for all samples in the temperature range 343-383 K, confirming their semiconducting character. The DC conductivity exhibits thermally activated behavior consistent with the Arrhenius model. The calculated activation energies are 0.71 eV (Sb-based), 0.54 eV (Sn-based), and 0.40 eV (Bi-based). Although the Bi-containing compound shows the lowest activation energy, the overall conductivity decreases in the order (C6H9N2)2[Sb2Cl8] > (C6H9N2)2SnCl6 > (C6H9N2)3[BiCl6]. These findings highlight that metal-ion substitution represents an effective approach to modulate the electronic structure and charge transport properties of 2-amino-5-methylpyridinium-based hybrid materials, underscoring their potential for semiconducting and electronic device applications.

Multifunctional polyurethanes face a fundamental design trade-off: enhanced cross-linking and rigidity improve mechanical robustness but inevitably restrict chain mobility, thereby compromising essential features such as self-healing and recyclability. This inherent compromise severely constrains their multifunctional application. Here, we report a supramolecular polyurethane (COPUSL) comprising a "dynamic switch" constructed from dynamic disulfide bonds and hydrogen bonds, together with a "rigid-flexible balanced network" composed of castor oil long fatty chains and polyphenol-functionalized lignin. This design endows COPUSL with excellent mechanical properties while also enabling rapid self-healing (self-healing efficiency: 87%) and efficient recyclability. Furthermore, COPUSL with introduced aromatic structures and extended conjugate systems exhibits 100% ultraviolet-blocking efficiency and a high photothermal conversion capability (surface temperature: 153 &#xb0;C) due to the electron transition and energy release of the lignin structure after absorbing light energy. By systematically investigating the relaxation kinetics, dynamic behavior, and macroscopic properties, we elucidate the distinct roles of the "dynamic switch" and "rigid-flexible balanced network" in regulating the polymer architecture and connecting dynamic behavior with mechanical and functional performance. These findings provide molecular-level insights for the design of high-performance, bio-based polyurethane with tailored multifunctional responsiveness.

Structural interpretation of accurate experimental data becomes increasingly challenging when nonlocal effects become important, particularly in delocalized open-shell systems and flexible hydrogen-bonded molecules. In these regimes, density functional methods, even when augmented by bond corrections, become insufficient because the transferable unit of the structural error is defined at an inappropriate scale. Here, we show that transferable corrections can instead be formulated by shifting from individual bonds to larger interaction-driven building blocks. These can be identified automatically and assigned, in a black-box fashion, to the appropriate rung of a general accuracy ladder, thereby establishing a direct correspondence between the scale at which errors arise and the level of electronic-structure theory required to describe them, while retaining an affordable computational cost. Across radicals, nonplanar aromatic systems, and flexible hydrogen-bonded networks, quantitative agreement between theory and experiment is recovered only when the physically relevant transferable unit of the error is matched to a commensurate level of theory and vibrational averaging is treated consistently. Accurate structures are therefore obtained not by uniformly increasing the level of theory but by matching the scale of error transferability with the appropriate level of description. Within this framework, multilevel strategies naturally emerge for large systems in which different regions are treated at different rungs of the ladder according to their structural complexity. This enables available experimental rotational constants to be reproduced within &#x223c;0.1-0.2% at affordable cost, corresponding to root-mean-square deviations of atomic positions on the order of 1-2 &#xd7; 10-3 &#xc5;.

The aim of this study was to evaluate the long-term success rates of dental implants placed in pristine bone (PB) compared to those placed in sites with staged autogenous bone augmentation (ABA) over a 10-year follow-up. A retrospective study was conducted on 144 patients treated between 2012 and 2014. Patients were divided into two groups: PB or ABA. Clinical parameters including pain, mobility, exudation, and radiographic peri-implant bone loss were assessed. A total of 260 implants were evaluated, with 137 implants in the PB group and 123 in the ABA group. The mean follow-ups were 124.2 and 123.8 months, respectively. No significant difference was found between the two groups in terms of pain, mobility, and exudate. Marginal bone loss was significantly greater in the ABA group (1.5 mm) compared to the PB group (1.4 mm) (P = 0.014). The cumulative implant success rate at 10 years was 90.2% for ABA and 95.6% for PB, with no statistically significant difference between groups (P = 0.140). Within the ABA group, implants in horizontally augmented sites demonstrated a significantly higher success rate (98.9%) compared to those in vertically augmented sites (65%) (P < 0.001). Implants in vertically augmented sites exhibited greater bone loss (1.8 mm) compared to horizontally augmented sites (1.5 mm) (P = 0.018). Long-term success rates of implants in augmented sites were consistent with those in pristine bone. Further studies with standardized parameters are needed to identify factors influencing clinical outcomes.

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Local anesthetic solutions containing epinephrine are widely used in oral surgery to prolong anesthesia and improve hemostasis; however, their sympathomimetic effects may influence cardiovascular parameters. Evidence comparing different epinephrine concentrations in articaine during third-molar surgery remains limited. This randomized clinical trial compared the cardiovascular effects and clinical performance of 4% articaine with epinephrine 1:100,000 (A100) and 1:200,000 (A200) during mandibular third-molar extraction. A prospective, randomized, split-mouth, double-blind clinical trial was conducted in 40 healthy patients undergoing bilateral impacted mandibular third-molar extraction. Each participant received A100 on one side and A200 on the contralateral side in randomized order with a 15-day interval. Heart rate (HR), blood pressure (BP), and oxygen saturation (SpO2) were recorded at baseline, immediately after injection, and at 5 and 15 minutes. Intraoperative bleeding, pain (VAS), and need for supplemental anesthesia were also assessed. Paired statistical tests were applied ( = 0.05). Eighty procedures were analyzed. Intraoperative bleeding incidence was similar between A100 (10%) and A200 (12.5%) (p = 1.000). Supplemental anesthesia was required in 3.8% of procedures, with no difference between concentrations (p = 1.000). HR increased with both formulations but was significantly higher with A100 at 5 and 15 minutes (p = 0.035 and p = 0.003). BP showed no significant differences at any time point. SpO2 remained within normal limits, with slightly higher values for A200 at intermediate times. Pain scores did not differ significantly. Both epinephrine concentrations in 4% articaine provided comparable anesthetic efficacy and hemostasis with minimal cardiovascular effects in healthy patients undergoing mandibular third-molar extraction. The 1:200,000 concentration produced a smaller heart-rate increase, suggesting a potential advantage in patients with cardiovascular risk, while 1:100,000 remains suitable when greater vasoconstriction is desired.

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