Botulinum neurotoxin type-A (BoNT-A) blocks the release of acetylcholine from peripheral cholinergic nerve terminals and is an important option for the treatment of disorders characterised by excessive cholinergic neuronal activity. Several BoNT-A products are currently marketed, each with unique manufacturing processes, excipients, formulation, and non-interchangeable potency units. Nevertheless, the effects of all the products are mediated by the 150 kDa BoNT-A neurotoxin. We assessed the quantity and light chain (LC) activity of BoNT-A in three commercial BoNT-A products (Dysport^®; Botox^®; Xeomin^®). We quantified 150 kDa BoNT-A by sandwich ELISA and assessed LC activity by EndoPep assay. In both assays, we assessed the results for the commercial products against recombinant 150 kDa BoNT-A. The mean 150 kDa BoNT-A content per vial measured by ELISA was 2.69 ng/500 U vial Dysport^®, 0.90 ng/100 U vial Botox^®, and 0.40 ng/100 U vial Xeomin^®. To present clinically relevant results, we calculated the 150 kDa BoNT-A/US Food and Drug Administration (FDA)-approved dose in adult upper limb spasticity: 5.38 ng Dysport^® (1000 U; 2 × 500 U vials), 3.60 ng Botox^® (400 U; 4 × 100 U vials), and 1.61 ng Xeomin^® (400 U; 4 × 100 U vials). EndoPep assay showed similar LC activity among BoNT-A products. Thus, greater amounts of active neurotoxin are injected with Dysport^®, at FDA-approved doses, than with other products. This fact might explain the long duration of action reported across multiple indications, which benefits patients, caregivers, clinicians, and healthcare systems.

The perceived threat of the use of nerve agents by terrorists against civilian targets implies the need for methods for point-of-care (POC) diagnosis. This review presents an overview of methods that are currently available for the assessment of exposure to nerve agents. Since these methods are mostly MS based, they require complex and expensive equipment and well-trained personnel and, consequently, they are not very suitable for rapid POC diagnosis. However, new technologies are emerging that allow, among others, immunochemical detection of acetylcholinesterase inhibited by nerve agents. Also, lab-on-a-chip methodologies are under development. It is anticipated that MS methods will be suitable for POC diagnosis within a few years, due to the miniaturization of equipment and the emergence of methodologies that enable mass spectrometric analysis with little sample pretreatment and that are potentially fieldable, such as direct analysis in real time and desorption electrospray ionization MS.

Armed forces typically have personal protective clothing (PPC) in place to offer protection against chemical, biological, radiological and nuclear (CBRN) agents. The regular soldier is equipped with permeable CBRN-PPC. However, depending on the operational task, these PPCs pose too much thermal strain to the wearer, which results in a higher risk of uncompensable heat stress. This study investigates the possibilities of adjustable CBRN-PPC, consisting of different layers that can be worn separately or in combination with each other. This novel concept aims to achieve optimization between protection and thermal strain during operations. Two CBRN-PPC (protective) layers were obtained from two separate manufacturers: (i) a next-to-skin (NTS) and (ii) a low-burden battle dress uniform (protective BDU). In addition to these layers, a standard (non-CBRN protective) BDU (sBDU) was also made available. The effect of combining clothing layers on the levels of protection were investigated with a Man-In-Simulant Test. Finally, a mechanistic numerical model was employed to give insight into the thermal burden of the evaluated CBRN-PPC concepts. Combining layers results in substantially higher protection that is more than the sum of the individual layers. Reducing the airflow on the protective layer closest to the skin seems to play an important role in this, since combining the NTS with the sBDU also resulted in substantially higher protection. As expected, the thermal strain posed by the different clothing layer combinations decreases as the level of protection decreases. This study has shown that the concept of adjustable protection and thermal strain through multiple layers of CBRN-PPC works. Adjustable CBRN-PPC allows for optimization of the CBRN-PPC in relation to the threat level, thermal environment, and tasks at hand in an operational setting.

The authors wish to make the following corrections to their paper