Network of cyano-p-aramid nanofibres creates ultrastiff and water-rich hydrospongels.

The structure-property paradox of biological tissues, in which water-rich porous structures efficiently transfer mass while remaining highly mechanically stiff, remains unsolved. Although hydrogel/sponge hybridization is the key to understanding this phenomenon, material incompatibility makes this a challenging task. Here we describe hydrogel/sponge hybrids (hydrospongels) that behave as both ultrastiff water-rich gels and reversibly squeezable sponges. The self-organizing network of cyano-p-aramid nanofibres holds approximately 5,000 times more water than its solid content. Hydrospongels, even at a water concentration exceeding 90 wt%, are hard as cartilage with an elastic modulus of 50-80 MPa, and are 10-1,000 times stiffer than typical hydrogels. They endure a compressive strain above 85% through poroelastic relaxation and hydrothermal pressure at 120 °C. This performance is produced by amphiphilic surfaces, high rigidity and an interfibrillar, interaction-driven percolating network of nanofibres. These features can inspire the development of future biofunctional materials.

Microtoxin for Improving Pore Size, Skin Laxity, Sebum Control, and Scars: A Roundtable on Integrating Intradermal Botulinum Toxin Type A Microdoses Into Clinical Practice.

BACKGROUND: In aesthetic clinical practice, botulinum toxin type A (BoNT-A) is best known for its use as a neuromodulator for the treatment of dynamic facial lines; however, when injected intradermally as microdroplets, BoNT-A can improve skin quality and overall skin appearance. OBJECTIVES: To discuss key aspects of microtoxin use in clinical practice and provide expert guidance on utilization. METHODS: As part of a continuing medical education lecture series and roundtable, the authors discussed key aspects of microtoxin patient selection, injection technique, and safety. RESULTS: The experiences of expert faculty are shared here. Clinical experience is consistent with reported data. Microtoxin can be used to reduce pore size, sebum production, rosacea, acne, and fine lines, and to improve jawline and neck definition. Intradermal injection can also be employed for the improvement of transverse neck lines as well as for the safe prevention and management of scars and keloids. CONCLUSIONS: Expanding the use of BoNT-A, a predictable, minimally invasive, and affordable treatment to address commonly encountered complaints is appealing. The authors have found that making patients aware of microtoxin as a treatment option results in an increased interest in and utilization of BoNT-A, and high satisfaction among appropriately selected patients.

Intradermal Microdroplet Injection of Diluted Incobotulinumtoxin-A for Sebum Control, Face Lifting, and Pore Size Improvement.

BACKGROUND: Intradermal injections of botulinum toxin have been reported to improve sebum secretion, facial skin laxity, and facial pores. However, the effects of Incobotulinumtoxin-A for these indications have not been reported. OBJECTIVE: To evaluate the efficacy of Incobotulinumtoxin-A for the improvement of sebum secretion, face laxity, and facial pores. MATERIALS AND METHODS: This single-center retrospective study included patients treated with Incobotulinumtoxin-A to improve facial skin laxity, sebum secretion, and facial pores. The microdroplet injection protocol included injection points on the lateral face, anterior medial cheek, mandibular line, depressor anguli oris points, mid-glabella area, and chin. Outcomes were measured using a Sebumeter and three-dimensional scanner and were evaluated by facial laxity ratings and the Global Aesthetic Improvement Scale. RESULTS: Twenty patients were included in the analysis. Sebum secretion, mandibular length, facial pores, and facial laxity ratings were improved at 1 week and results were sustained through 12 weeks. All outcomes showed maximum improvement after 4 weeks. Evaluation using the Global Aesthetic Improvement Scale showed that all subjects reported at least a score of 2 (improved) after 4 weeks. CONCLUSION: This study showed that intradermal injection with Incobotulinumtoxin-A could be effective for face lifting, reduced sebum production, and improved facial pores. J Drugs Dermatol. 2021;20(1):49-54. doi:10.36849/JDD.5616.

Homochiral Supramolecular Thin Film from Self-Assembly of Achiral Triarylamine Molecules by Circularly Polarized Light.

Here, we report the formation of homochiral supramolecular thin film from achiral molecules, by using circularly polarized light (CPL) only as a chiral source, on the condition that irradiation of CPL does not induce a photochemical change of the achiral molecules. Thin films of self-assembled structures consisting of chiral supramolecular fibrils was obtained from the triarylamine derivatives through evaporation of the self-assembled triarylamine solution. The homochiral supramolecular helices with the desired handedness was achieved by irradiation of circularly polarized visible light during the self-assembly process, and the chiral stability of supramolecular self-assembled product was achieved by photopolymerization of the diacetylene moieties at side chains of the building blocks, with irradiation of circularly polarized ultraviolet light. This work provides a novel methodology for the generation of homochiral supramolecular thin film from the corresponding achiral molecules.

Study on the Synthetic Characteristics of Biomass-Derived Isosorbide-Based Poly(arylene ether ketone)s for Sustainable Super Engineering Plastic.

Demand for the development of novel polymers derived from biomass that can replace petroleum resources has been increasing. In this study, biomass-derived isosorbide was used as a monomer in the polymerization of poly(arylene ether ketone)s, and its synthetic characteristics were investigated. As a phase-transfer catalyst, crown ether has increased the weight-average molecular weight of polymers over 100 kg/mol by improving the reaction efficiency of isosorbide and minimizing the effect of moisture. By controlling the experimental parameters such as halogen monomer, polymerization solvent, time, and temperature, the optimal conditions were found to be fluorine-type monomer, dimethyl sulfoxide, 24 h, and 155 °C, respectively. Biomass contents from isosorbide-based polymers were determined by nuclear magnetic resonance and accelerator mass spectroscopy. The synthesized polymer resulted in a high molecular weight that enabled the preparation of transparent polymer films by the solution casting method despite its weak thermal degradation stability compared to aromatic polysulfone. The melt injection molding process was enabled by the addition of plasticizer. The tensile properties were comparable or superior to those of commercial petrochemical specimens of similar molecular weight. Interestingly, the prepared specimens exhibited a significantly lower coefficient of thermal expansion at high temperatures over 150 °C compared to polysulfone.

Efficacy and Tolerability of IncobotulinumtoxinA for Treating Glabellar Frown Lines in Korean Adults: A Postmarketing Observational Study.

BACKGROUND: IncobotulinumtoxinA is safe and effective in Caucasian adults. Its effects have been less documented in Asian adults. OBJECTIVE: To describe the efficacy and tolerability of incobotulinumtoxinA for treating glabellar frown lines (GFLs) in South Korean adults. METHODS: South Korean adults aged 18 to 65 years with moderate-to-severe GFLs received a single dose of 10 to 28 U incobotulinumtoxinA during routine clinical practice. After 30 ± 14 days, investigators assessed the efficacy using the Global Aesthetic Improvement Scale and rated tolerability using a 4-point scale. RESULTS: Six hundred seventy-three subjects were enrolled, of which 528 completed the study according to protocol. Glabellar frown lines improved in 98.7% (521/528) of subjects, with 30.8% of cases rated as "very much improved" and 47.4% as "much improved." The extent of improvement was unaffected by sex, age, and weight but was greater when the time between GFL identification and treatment was <6 months (p < .001) and when concomitant aesthetic nondrug treatments were used (p < .001). For 94% of subjects, tolerability was good or very good. All reported adverse events were transient and mild or moderate in severity. CONCLUSION: IncobotulinumtoxinA was well tolerated and effective for treating moderate-to-severe GFLs in Korean adults irrespective of age, sex, or weight.

Practical Applications of Self-Healing Polymers Beyond Mechanical and Electrical Recovery.

Self-healing polymeric materials, which can repair physical damage, offer promising prospects for protective applications across various industries. Although prolonged durability and resource conservation are key advantages, focusing solely on mechanical recovery may limit the market potential of these materials. The unique physical properties of self-healing polymers, such as interfacial reduction, seamless connection lines, temperature/pressure responses, and phase transitions, enable a multitude of innovative applications. In this perspective, the diverse applications of self-healing polymers beyond their traditional mechanical strength are emphasized and their potential in various sectors such as food packaging, damage-reporting, radiation shielding, acoustic conservation, biomedical monitoring, and tissue regeneration is explored. With regards to the commercialization challenges, including scalability, robustness, and performance degradation under extreme conditions, strategies to overcome these limitations and promote successful industrialization are discussed. Furthermore, the potential impacts of self-healing materials on future research directions, encompassing environmental sustainability, advanced computational techniques, integration with emerging technologies, and tailoring materials for specific applications are examined. This perspective aims to inspire interdisciplinary approaches and foster the adoption of self-healing materials in various real-life settings, ultimately contributing to the development of next-generation materials.

Preparation of a nanocellulose/nanochitin coating on a poly(lactic acid) film for improved hydrolysis resistance.

Growing concerns regarding plastic waste have prompted various attempts to replace plastic packaging films with biodegradable alternatives such as poly(lactic acid) (PLA). However, their low hydrolysis resistance owing to the presence of aliphatic polyesters limits the shelf life of biodegradable polymers. Hydrolysis leads to the deterioration of mechanical performance, which is a key disadvantage of biodegradable plastics. In this study, a layer-by-layer (LBL) assembly method was used for the dip-coating of biorenewable, biodegradable nanocellulose/nanochitin on the PLA surface. Additional crosslinking and compression of the coated nanofibers, each containing carboxylic acid and amine groups, respectively, were induced through electromagnetic microwave irradiation to protect the PLA film by improving hydrolysis resistance. The coatings were examined by morphological observations and water contact angle measurements. The LBL coatings of differently charged nanofibers of 10.6 µm were reduced to 40 % after microwave treatment, and the thickness does not vary after the hydrolysis experiment. Microwave irradiation increased the water contact angle owing to amide linkage formation, thereby preventing the peeling off of coating layers. Improved hydrolysis resistance inhibited the reduction in molecular weight and tensile strength. These findings could be used to develop sustainable and biodegradable plastic packaging films with a prolonged shelf life.

Next-generation all-organic composites: A sustainable successor to organic-inorganic hybrid materials.

This Review presents an overview of all-organic nanocomposites, a sustainable alternative to organic-inorganic hybrids. All-organic nanocomposites contain nanocellulose, nanochitin, and aramid nanofibers as highly rigid reinforcing fillers. They offer superior mechanical properties and lightweight characteristics suitable for diverse applications. The Review discusses various methods for preparing the organic nanofillers, including top-down and bottom-up approaches. It highlights in situ polymerization as the preferred method for incorporating these nanomaterials into polymer matrices to achieve homogeneous filler dispersion, a crucial factor for realizing desired performance. Furthermore, the Review explores several applications of all-organic nanocomposites in diverse fields including food packaging, performance-advantaged plastics, and electronic materials. Future research directions-developing sustainable production methods, expanding biomedical applications, and enhancing resistance against heat, chemicals, and radiation of all-organic nanocomposites to permit their use in extreme environments-are explored. This Review offers insights into the potential of all-organic nanocomposites to drive sustainable growth while meeting the demand for high-performance materials across various industries.

Structural evaluation of Poly(lactic acid) degradation at standardized composting temperature of 58 degrees.

The accumulation of petroleum-based plastics on our planet is causing serious environmental pollution. Biodegradable plastics, promoted as eco-friendly solutions, hold the potential to address this issue. However, their impact on the environment and the mechanisms of their natural degradation remain inadequately understood. Furthermore, the specific conditions set forth in international standards for evaluating the biodegradability of biodegradable plastics have led to misconceptions about their real-world behavior. To properly elucidate the relationship between their degradability and structure, this study mimics the thermal effect on poly(lactic acid) (PLA) under standardized composting temperature. The higher the crystallinity of PLA, the lower the degradation rate, which suggests that crystallinity is a key factor in determining degradation. The composting temperature of 58 °C induces crystallization by having a structural effect on the polymer, which in turn reduces the degradation rate of PLA. Therefore, control over temperature and crystallization during the processing and degradation of PLA is crucial, as it not only determines the biodegradability but also enhances the utility.

Real-world Implications of Botulinum Neurotoxin A Immunoresistance for Consumers and Aesthetic Practitioners: Insights from ASCEND Multidisciplinary Panel.

Background: As long-term, regular aesthetic botulinum neurotoxin A (BoNT-A) use becomes more commonplace, it is vital to understand real-world risk factors and impact of BoNT-A immunoresistance. The first Aesthetic Council on Ethical Use of Neurotoxin Delivery panel discussed issues relating to BoNT-A immunoresistance from the health care professionals' (HCPs') perspective. Understanding the implications of BoNT-A immunoresistance from the aesthetic patient's viewpoint allows HCPs to better support patients throughout their aesthetic treatment journey. Methods: A real-world consumer study surveyed 363 experienced aesthetic BoNT-A recipients across six Asia-Pacific territories. The survey mapped participants' BoNT-A aesthetic treatment journey and characterized awareness and attitudes relating to BoNT-A immunoresistance and treatment implications. At the second Aesthetic Council on Ethical use of Neurotoxin Delivery meeting, panelists discussed survey findings and developed consensus statements relating to the impact of BoNT-A immunoresistance on the aesthetic treatment journey. Results: Aesthetic BoNT-A patients' depth of knowledge about BoNT-A immunoresistance remains low, and risk/benefit communications need to be more lay-friendly. The initial consultation is the most important touchpoint for HCPs to raise awareness of BoNT-A immunoresistance as a potential side effect considering increased risk with repeated high-dose treatments. HCPs should be cognizant of differences across BoNT-A formulations due to the presence of certain excipients and pharmacologically unnecessary components that can increase immunogenicity. Standardized screening for clinical signs of secondary nonresponse and a framework for diagnosing and managing immunoresistance-related secondary nonresponse were proposed. Conclusion: These insights can help patients and HCPs make informed treatment decisions to achieve desired aesthetic outcomes while preserving future treatment options with BoNT-A.

Treatment Protocol on Using Microfocused Ultrasound with Visualization for Skin Quality Improvement: The Korean Experience.

Facial skin quality profoundly influences an individual's perceived appearance and is an important aspect of facial rejuvenation. Facial pore enlargement is one of the most common concerns among Asian individuals that adversely impacts perceived skin surface evenness and affects overall skin quality. One of the major causes of enlarged pores is facial skin laxity. Microfocused ultrasound with visualization (MFU-V; Ultherapy; Merz North America, Inc., Raleigh, N.C.) is indicated for lifting and tightening of the face and neck, and improving the appearance of wrinkles on the décolletage. In addition, it is useful for addressing several aspects of facial rejuvenation, including facial pores, skin laxity, skin unevenness, etc., but there is limited literature on these applications. Thus, we present our proposed MFU-V treatment protocol for achieving a harmonious outcome for attractive skin, along with practical strategies for its application, illustrated in patients presenting with enlarged pores as their main concern. Drawing on our collective experience in using MFU-V for facial rejuvenation and the recently published skin quality framework that advocates addressing interrelated attributes of skin quality for optimal outcomes, we developed a treatment protocol for improving skin quality using MFU-V. This MFU-V treatment protocol reliably improves overall skin quality in patients presenting with enlarged pores, through MFU-V's effects on skin lifting and tightening, and consequent improvement in facial pores and skin texture. This treatment protocol can be readily used as part of a multimodal layering approach to yield successful outcomes in patients with various facial skin concerns.

Combined Treatment with Micro-Focused Ultrasound with Visualization and Intradermal Incobotulinumtoxin-A for Enlarged Facial Pores: A Retrospective Study in Asians.

Background: Despite the increasing need for the improvement of enlarged facial pores, the treatment remains challenging. A few previous studies have reported the effects of micro-focused ultrasound with visualization (MFU-V) or intradermal incobotulinumtoxin-A (INCO) on enlarged facial pores. Objective: To evaluate the efficacy and safety of combined treatment with superficial MFU-V and intradermal INCO for enlarged facial pores. Methods: This single-center retrospective study included 20 patients treated with MFU-V and intradermal INCO to improve enlarged facial pores. Outcomes were evaluated 1, 4, 12, and 24 weeks after a single session of the combined procedure. Pore count and density were objectively quantitated using a three-dimensional scanner, and improvement was assessed using the physician and patient Global Aesthetic Improvement Scale (GAIS). Results: The mean pore count and density decreased after one week and decreased by up to 62% until 24 weeks. After one week, almost all patients (100% in physician GAIS and 95% in patient GAIS) showed improvement with a grade 3 (much improved) or higher. All adverse events were transient. Conclusion: Combined treatment with MFU-V and intradermal INCO could be effective and safe for reducing enlarged facial pores; the improvements can be sustained for up to 24 weeks.

Nanochitin and Nanochitosan: Chitin Nanostructure Engineering with Multiscale Properties for Biomedical and Environmental Applications.

Nanochitin and nanochitosan (with random-copolymer-based multiscale architectures of glucosamine and N-acetylglucosamine units) have recently attracted immense attention for the development of green, sustainable, and advanced functional materials. Nanochitin and nanochitosan are multiscale materials from small oligomers, rod-shaped nanocrystals, longer nanofibers, to hierarchical assemblies of nanofibers. Various physical properties of chitin and chitosan depend on their molecular- and nanostructures; translational research has utilized them for a wide range of applications (biomedical, industrial, environmental, and so on). Instead of reviewing the entire extensive literature on chitin and chitosan, here, recent developments in multiscale-dependent material properties and their applications are highlighted; immune, medical, reinforcing, adhesive, green electrochemical materials, biological scaffolds, and sustainable food packaging are discussed considering the size, shape, and assembly of chitin nanostructures. In summary, new perspectives for the development of sustainable advanced functional materials based on nanochitin and nanochitosan by understanding and engineering their multiscale properties are described.

Aesthetic considerations for treating the Asian patient: Thriving in diversity international roundtable series.

BACKGROUND: The unique anatomy of the Asian face, along with the influence of cultural forces and regional preferences, has led to the development of specialized approaches to rejuvenation and beautification that are applicable to the aesthetic practice within Asia as well as those who serve these patients internationally. AIMS: To discuss similarities and differences in anatomy and treatment preferences of Asian patients and explore how these differences may influence aesthetic practices. PATIENTS/METHODS: In support of clinicians who wish to serve a diverse patient population, a six-part international roundtable series focused on diversity in aesthetics was conducted from August 24, 2021 to May 16, 2022. RESULTS: The results of the sixth and final roundtable in the series, the Asian Patient, are described here. Anatomical differences and their influence on treatment preferences are discussed, and specific procedural information provided for management of facial shape and projection, including advanced injection techniques for the eyelid-forehead complex. CONCLUSIONS: The continued exchange of ideas and treatment techniques support not only optimal aesthetic outcomes for a diverse range of patients within a given practice, but also the evolution of aesthetic medicine. The expert approaches detailed here may be used to inform treatment plans tailored to the Asian population.

Review of polymer technologies for improving the recycling and upcycling efficiency of plastic waste.

Human society has become increasingly reliant on plastic because it allows for convenient and sanitary living. However, recycling rates are currently low, which means that the majority of plastic waste ends up in landfills or the ocean. Increasing recycling and upcycling rates is a critical strategy for addressing the issues caused by plastic pollution, but there are several technical limitations to overcome. This article reviews advancements in polymer technology that aim to improve the efficiency of recycling and upcycling plastic waste. In food packaging, natural polymers with excellent gas barrier properties and self-cleaning abilities have been introduced as environmentally friendly alternatives to existing materials and to reduce food-derived contamination. Upcycling and valorization approaches have emerged to transform plastic waste into high-value-added products. Recent advancements in the development of recyclable high-performance plastics include the design of super engineering thermoplastics and engineering chemical bonds of thermosets to make them recyclable and biodegradable. Further research is needed to develop more cost-effective and scalable technologies to address the plastic pollution problem through sustainable recycling and upcycling.

Method to analyze phthalate esters from soft toys dissolving into water mimicking infant playing.

Along with bisphenol-A (BPA), conventional phthalate esters (PAEs) have been reported as environmental hormones, despite their functional usefulness as plasticizers. Nevertheless, they are frequently found in various products, including children's utensils and toys made of poly (vinyl chloride). This is tremendously important because PAEs are harmful to infants. In addition, gel/slime-type toys made of poly (vinyl alcohol) are currently popular for developing infant' tactile senses. In this study, we developed a method to qualitatively and quantitatively detect PAEs in gel/slime-type toys mimicking, infants playing with them in a bathtub. As a result, 1,2-cyclohexanedicarboxylic acid diisononyl ester (DINCH), one of the PAE alternatives, transferred into the water from the toys and was detected most commonly (108-719 µg g-1; 0.01-0.07 wt%) among PAEs. The detected DINCH levels were below the universally accepted levels for PAEs (0.1 wt%). However, the amount of DINCH detected could still be toxic, in accordance with toxicity tests using water fleas. Furthermore, unpleasant odors were emitted when the toys containing toxic volatile organic compounds were unpacked. This is the first study to develop a method to analyze PAE in gel/slime-type toys and determine that alternatives to conventional PAEs cannot be unconditionally regarded as safe chemicals. Therefore, the revised standards for regulating PAEs and their alternatives must be reconsidered.

Circular waste management: Superworms as a sustainable solution for biodegradable plastic degradation and resource recovery.

Bioplastics offer a promising solution to plastic pollution, however, their production frequently relies on edible biomass, and their degradation rates remain inadequate. This study investigates the potential of superworms (Zophobas atratus larvae) for polybutylene succinate (PBS) waste management, aiming to achieve both resource recovery and biodegradation. Superworms exclusively fed on PBS for a month exhibited the same survival rate as those on a standard bran diet. PBS digestion yielded a 5.13% weight gain and a 23.23% increase in protein composition in superworms. Additionally, carbon isotope analyses substantiated the conversion of PBS into superworm components. Gut microbes capable of PBS biodegradation became progressively prominent, further augmenting the degradation rate of PBS under composting conditions (ISO 14855-1). Gut-free superworms fed with PBS exhibited antioxidant activities comparable to those of blueberries, renowned for their high antioxidant activity. Based on these findings, this study introduces a sustainable circular solution encompassing recycling PBS waste to generate insect biomass, employing insect gut and frass for PBS degradation and fertilizer, and harnessing insect residue as a food source. In essence, the significance of this research extends to socio-economic and environmental spheres, impacting waste management, resource efficiency, circular economy promotion, environmental preservation, industrial advancement, and global sustainability objectives. The study's outcomes possess the potential to reshape society's approach to plastic waste, facilitating a shift toward more sustainable paradigms.

Self-assembly driven by an aromatic primary amide motif.

Primary amides are unique supramolecular synthons possessing two hydrogen donors and two hydrogen acceptors. By interacting in a complementary fashion, primary amides reliably generate two-dimensional hydrogen bonded networks that differ from conventional hydrogen bonded structures such as carboxylic acid dimers or one-dimensional secondary amide chains. This feature permits the design of sophisticated supramolecular assemblies based on primary amides (especially aromatic amides). Several interesting crystal structures have been constructed utilizing primary amides, although such structures have been applied only in the field of crystal engineering because the networks strongly favor crystallization. Expansion of the applications of primary amides to liquid crystals and self-assembly in solution requires an appropriate balance between primary amide-based hydrogen bonding and other noncovalent interactions. This perspective article reviews the key hydrogen bonding properties of primary amides determined from crystal structure studies, and a variety of supramolecular assemblies involving primary amides are discussed. A new strategy for overcoming crystallinity and solubility issues is proposed, involving introduction of a trifluoromethyl group at the ortho position of the aromatic primary amide. Such substitutions produce highly processable primary amides, while maintaining the two-dimensional hydrogen bonded network. Examples of self-assembly using 2-trifluoromethylbenzamide demonstrate its usefulness in self-assembly.

Immunogenicity Associated with Aesthetic Botulinumtoxin A: A Survey of Asia-Pacific Physicians' Experiences and Recommendations.

Background: Most botulinum toxin A (BoNT/A) products contain unnecessary bacterial components that increase the risk of developing neutralizing antibodies (nAbs). Reports of secondary nonresponse and treatment failures (STF) due to nAbs have accompanied a surge in new BoNT/A products. Methods: To formulate recommendations on managing toxin resistance, we reviewed the evidence on BoNT/A-associated immunogenicity and evaluated Asian physicians' current BoNT/A practices, knowledge, and real-world experiences, as provided by survey outcomes conducted with 128 Asian experts (regular botulinum toxin injectors). Results: Most doctors believe STF occurs, some patients exhibit partial symptoms, and impurities (eg, complexing proteins) in BoNT/A preparations risk STF. Bioassays that distinguish non-nAbs from nAbs that hinder toxin function remain unavailable to most doctors, though most would perform testing if given the option. Doctors in the Asia-Pacific region have differing strategies for managing STF, depending on the availability of alternatives or tests. They recommended switching to a highly-purified formulation free of complexing proteins and other impurities to lower the risk of immunogenicity, or offering treatment holidays of 2 -2.5 years. They suggested restarting treatment with the same highly purified formulation, especially for repeated treatments, large-dose injections, and younger patients who will accumulate higher lifetime doses, so as to minimize immunogenic risks and preserve long-term treatment outcomes. Importantly, doctors should always initiate patients on pure formulations rather than switching to these only after resistance develops. Conclusion: Choosing highly purified BoNT/A products at treatment initiation enhances long-term efficacy and patient satisfaction while minimizing the risk of immune activation and nAb formation.