Pregnancy is a particularly vulnerable period for the growing fetus, when exposure to toxic agents, especially in the early phases, can decisively harm embryo development and compromise the future health of the newborn. The inclusion of various chemical substances in personal care products (PCPs) and cosmetic formulations can be associated with disruption and damage to the nervous system. Microplastics, benzophenones, parabens, phthalates and metals are among the most common chemical substances found in cosmetics that have been shown to induce neurotoxic mechanisms. Although cosmetic neurotoxin exposure is believed to be minimal, different exposure scenarios of cosmetics suggest that these neurotoxins remain a threat. Special attention should be paid to early exposure in the first weeks of gestation, when critical processes, like the migration and proliferation of the neural crest derived cells, start to form the ENS. Importantly, cosmetic neurotoxins can cross the placental barrier and affect the future embryo, but they are also secreted in breast milk, so babies remain exposed for longer periods, even after birth. In this review, we explore how neurotoxins contained in cosmetics and PCPs may have a role in the pathogenesis of various neurodevelopmental disorders and neurodegenerative diseases and, therefore, also in congenital enteric aganglionosis as well as in postnatal motility disorders. Understanding the mechanisms of these chemicals used in cosmetic formulations and their role in neurotoxicity is crucial to determining the safety of use for cosmetic products during pregnancy.

BACKGROUND: There are 7 known serotypes of botulinum neurotoxins (A through G). Currently, commercially available toxins are those in serotypes A and B. This paper will discuss new toxins on the horizon, developments in prolonging and shortening the duration of outcomes, and novel therapeutic indications on the horizon.
OBJECTIVE: To provide insight into new toxins and new therapeutic modalities surrounding toxins on the horizon.
METHODS: The authors have reviewed the relevant literature and shared their insights and opinions as to future developments in toxin research and potential clinical applications.
CONCLUSIONS: Botulinum neurotoxin type E\'s faster onset and shorter duration of effect represent true clinical differentiators. Future development of botulinum neurotoxin type E for aesthetic and therapeutic uses will be in areas where fast onset and short duration of effect are desirable. Current challenges with neuromodulators include the need for frequent treatments and lack of reversal agents. Agents to address both challenges and novel indications, including inhibition of melanogenesis, are being developed.

BACKGROUND: Facial aging involves multilevel changes, extending from the skin to deep support structures. A comprehensive treatment approach targeting the many aspects of facial dynamics and architecture is often necessary to achieve optimal correction, prevent changes before they occur, and/or help highlight inherited features.
OBJECTIVE: To explore the integration of botulinum toxin type A (BoNT-A) into multimodal aesthetic treatment plans.
METHODS: This article reviews evidence supporting the combination of BoNT-A with other minimally invasive cosmetic therapies, including dermal fillers, lasers, and energy-based devices as well as with plastic and reconstructive surgeries for more controlled healing and improved scar cosmesis.
RESULTS: Combination treatment protocols including BoNT-A demonstrate higher patient satisfaction and retention rates compared to monotherapy or sequential treatments. Some guidelines for sequencing of treatments exist, but evidence is scant with certain combinations.
CONCLUSIONS: Integrating BoNT-A into a larger aesthetic treatment plan is crucial for achieving natural and satisfying results in facial rejuvenation. Evidence supports better outcomes when incorporating with both surgical and nonsurgical modalities. Understanding how to address anatomy over time through different aesthetic therapies together allows for individually tailored, more deeply impactful treatment plans.

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HxTx-Hv1h, a neurotoxic peptide derived from spider venom, has been developed for use in commercial biopesticide formulations. Cell Penetrating Peptides (CPPs) are short peptides that facilitate the translocation of various biomolecules across cellular membranes. Here, we evaluated the aphidicidal efficacy of a conjugated peptide, HxTx-Hv1h/CPP-1838, created by fusing HxTx-Hv1h with CPP-1838. Additionally, we aimed to establish a robust recombinant expression system for HxTx-Hv1h/CPP-1838. We successfully achieved the secretory production of HxTx-Hv1h, its fusion with Galanthus nivalis agglutinin (GNA) forming HxTx-Hv1h/GNA and HxTx-Hv1h/CPP-1838 in yeast. Purified HxTx-Hv1h exhibited contact toxicity against Megoura crassicauda, with a 48 h median lethal concentration (LC50) of 860.5 μg/mL. Fusion with GNA or CPP-1838 significantly enhanced its aphidicidal potency, reducing the LC50 to 683.5 μg/mL and 465.2 μg/mL, respectively. The aphidicidal efficacy was further improved with the addition of surfactant, decreasing the LC50 of HxTx-Hv1h/CPP-1838 to 66.7 μg/mL-over four times lower compared to HxTx-Hv1h alone. Furthermore, we engineered HxTx-Hv1h/CPP-1838 multi-copy expression vectors utilizing the BglBrick assembly method and achieved high-level recombinant production in laboratory-scale fermentation. This study is the first to document a CPP fusion strategy that enhances the transdermal aphidicidal activity of a natural toxin like HxTx-Hv1h and opens up the possibility of exploring the recombinant production of HxTx-Hv1h/CPP-1838 for potential applications.

Neurotoxins pose significant challenges in defense and healthcare due to their disruptive effects on nervous tissues. Their extreme potency and enormous structural diversity have hindered the development of effective antidotes. Motivated by the properties of cell membrane-derived nanodiscs, such as their ultrasmall size, disc shape, and inherent cell membrane functions, here, we develop neuronal membrane-derived nanodiscs (denoted \"Neuron-NDs\") as a countermeasure nanomedicine for broad-spectrum neurotoxin detoxification. We fabricate Neuron-NDs using the plasma membrane of human SH-SY5Y neurons and demonstrate their effectiveness in detoxifying tetrodotoxin (TTX) and botulinum toxin (BoNT), two model toxins with distinct mechanisms of action. Cell-based assays confirm the ability of Neuron-NDs to inhibit TTX-induced ion channel blockage and BoNT-mediated inhibition of synaptic vesicle recycling. In mouse models of TTX and BoNT intoxication, treatment with Neuron-NDs effectively improves survival rates in both therapeutic and preventative settings. Importantly, high-dose administration of Neuron-NDs shows no observable acute toxicity in mice, indicating its safety profile. Overall, our study highlights the facile fabrication of Neuron-NDs and their broad-spectrum detoxification capabilities, offering promising solutions for neurotoxin-related challenges in biodefense and therapeutic applications.

BACKGROUND: The growing popularity of aesthetic procedures involving fillers, biostimulators, and neurotoxins has prompted concerns about patient safety. To address these concerns, a global Safety Task Force (STF) was formed.
OBJECTIVE: The inaugural STF meeting prioritized vascular compromise prevention and management, guiding clinical trial design and materials for future meetings, and collecting data from experts on current safety methods.
METHODS: The STF was formed and consisted of 16 experts from nine different countries, with each possessing distinct expertise in various fields related to aesthetic injectables. Current safety data, protocols, knowledge gaps and future research priorities were discussed and voted upon.
RESULTS: The establishment of a global database for tracking filler-related AEs was favored by 93% of participants. Discussions revolved around the database\'s scope, data standardization, and whether non-medical contributors should be included. Aspiration as a safety technique garnered support from 73% of participants. Approximately 43% of participants incorporate ultrasound in their injections, with divergent opinions on its impact and potential when used as a standard of practice versus in AE management. Most physicians on the task force incorporated cannula use for some of their injections (93%). There were varying perspectives on treatments for vascular adverse events (VAE), the primary causes, and the adoption of new protocols in the field.
CONCLUSIONS: The STF meeting underscored the need for a coordinated effort to address complications related to HA fillers, including VAE management and hyaluronidase protocols. Reliable treatment endpoints were evaluated, but improved measurement methods are needed. Future meetings will focus on addressing delayed complications, furthering safety in this field.

The neurotoxin β-N-methylamino-L-alanine (BMAA), produced by cyanobacteria and diatoms, has been implicated as an environmental risk factor for neurodegenerative diseases. This study first investigated the occurrence and monthly distributions of BMAA and its isomers, 2,4-diaminobutyric acid (DAB) and N-2-aminoethylglycine (AEG), in phytoplankton and mussels from 11 sites along the South Sea Coast of Korea throughout 2021. These toxins were quantified using LC-MS/MS, revealing elevated BMAA concentrations from late autumn to spring, with phase lags observed between phytoplankton and mussels. The highest concentration of BMAA in phytoplankton was detected in November (mean: 1490 ng g-1 dry weight (dw)), while in mussels, it peaked in December (mean: 1240 ng g-1 dw). DAB was detected in phytoplankton but was absent in mussels, indicating limited bioaccumulation potential. In February, the peak mean DAB concentration in phytoplankton was 89 ng g-1 dw. AEG was not detected in any samples. Chlorophyll-a concentrations consistently showed an inverse correlation with BMAA concentrations in mussels throughout the year. Through correlation analysis, four diatom genera, Bacillaria, Hemiaulus, Odontella, and Pleurosigma, were identified as potential causative microalgae of BMAA. This study offers insights into identifying the causative microalgae for BMAA and informs future regulatory efforts regarding unmanaged biotoxins.

Harmful algal blooms and the toxins produced during these events are a human and environmental health concern worldwide. Saxitoxin and its derivatives are potent natural aquatic neurotoxins produced by certain freshwater cyanobacteria and marine algae species during these bloom events. Saxitoxins effects on human health are well studied, however its effects on aquatic biota are still largely unexplored. This work aims at evaluating the effects of a pulse acute exposure (24 h) of the model cladoceran Daphnia magna to 30 μg saxitoxin L-1, which corresponds to the safety guideline established by the World Health Organization (WHO) for these toxins in recreational freshwaters. Saxitoxin effects were assessed through a comprehensive array of biochemical (antioxidant enzymes activity and lipid peroxidation), genotoxicity (alkaline comet assay), neurotoxicity (total cholinesterases activity), behavioral (swimming patterns), physiological (feeding rate and heart rate), and epigenetic (total 5-mC DNA methylation) biomarkers. Exposure resulted in decreased feeding rate, heart rate, total cholinesterases activity and catalase activity. Contrarily, other antioxidant enzymes, namely glutathione-S-transferases and selenium-dependent Glutathione peroxidase had their activity increased, together with lipid peroxidation levels. The enhancement of the antioxidant enzymes was not sufficient to prevent oxidative damage, as underpinned by lipid peroxidation enhancement. Accordingly, average DNA damage level was significantly increased in STX-exposed daphnids. Total DNA 5-mC level was significantly decreased in exposed organisms. Results showed that even a short-term exposure to saxitoxin causes significant effects on critical molecular and cellular pathways and modulates swimming patterns in D. magna individuals. This study highlights sub-lethal effects caused by saxitoxin in D. magna, suggesting that these toxins may represent a marked challenge to their thriving even at a concentration deemed safe for humans by the WHO.

UNASSIGNED: Cervical dystonia (CD) causes involuntary movements and postures of the head, neck, and shoulders, as well as nonmotor symptoms including pain, mood, and sleep dysfunction, and impacts quality of life. The first-line treatment for CD is botulinum neurotoxin (BoNT) injections.
UNASSIGNED: The clinical presentation and diagnosis of CD, as well as where BoNT resides in the treatment landscape, is reviewed first. Next, the mechanism of action and the pharmacological differences in the available preparations of BoNT products are explained. The evidence base for motor and nonmotor efficacy and safety of the available BoNT formulations is reviewed, with attention to duration of benefit as a driver of patient satisfaction. Practical determinants of BoNT efficacy are reviewed including muscle selection, accurate muscle injection, factors related to poor or deteriorating response, and immunogenicity.
UNASSIGNED: BoNT represents a significant advancement in the treatment of CD. More accurate diagnosis, muscle selection and targeting, and dosing can improve outcomes with existing BoNT formulations. Further refinement of BoNT potency, duration of action, safety, and immunogenicity will help reduce unmet needs in the magnitude and duration of benefit. Additional validation of DBS and MRI-guided focused ultrasound may expand options for patients with toxin nonresponse.