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Introduction: AIMS Myasthenia Gravis (MG) is an autoimmune neuromuscular disease in which patients suffer from recurrent exacerbation. There are insufficient data measuring the effects of the resources employed before and during acute exacerbation on subsequent disease outcomes. This study aims to identify factors which lead to lengthened hospital stay., Methods: This is a retrospective chart review of acute MG exacerbations requiring hospitalization. Exacerbations were identified using ICD-9/ICD-10 codes and considered the following variables: age and Myasthenia Gravis Foundation of America (MGFA) class at initial MG diagnosis, age and MGFA class at exacerbation, sex, thymectomy, cause of exacerbation, treatment regimen at time of exacerbation, inpatient treatment regimen, length of hospital stay (LOS), intubation, use of noninvasive ventilation, complications, and disposition., Results: Seventy patients with 141 hospitalizations were identified. Crisis management characterized by intubation and plasmapheresis positively correlated with LOS (both p < .001). Almost 1/5 hospitalizations required intubation. Previous thymectomy negatively correlated with LOS (p < .05). In contrast, male sex correlated with longer LOS (p < .05). One-third of hospital stays were followed by discharge to a post-acute care facility, 7% home with home health, and 1 hospitalization resulted in death., Discussion: Plasmapheresis, intubation, and male sex were associated with increased LOS in acute MG exacerbation. Intubation appears to be the strongest predictor of LOS. Those with previous thymectomy had shorter hospital stays. The role of thymectomy in the acute setting merits further analysis., (© 2023. The Author(s).)

Serum albumin (SA), the most abundant soluble protein in the body, maintains plasma oncotic pressure and regulates the distribution of vascular fluid and has a range of other important functions. The goals of this review are to expand clinical knowledge regarding the functions of SA, elucidate effects of dysregulated SA concentration, and discuss the clinical relevance of hypoalbuminemia resulting from various diseases. We discuss potential repercussions of SA dysregulation on cholesterol levels, liver function, and other processes that rely on its homeostasis, as decreased SA concentration has been shown to be associated with increased risk for cardiovascular disease, hyperlipidemia, and mortality. We describe the anti-inflammatory and antioxidant properties of SA, as well as its ability to bind and transport a plethora of endogenous and exogenous molecules. SA is the primary serum protein involved in binding and transport of drugs and as such has the potential to affect, or be affected by, certain medications. Of current relevance are antibody-based inhibitors of the neonatal Fc receptor (FcRn), several of which are under clinical development to treat immunoglobulin G (IgG)-mediated autoimmune disorders; some have been shown to decrease SA concentration. FcRn acts as a homeostatic regulator of SA by rescuing it, as well as IgG, from intracellular degradation via a common cellular recycling mechanism. Greater clinical understanding of the multifunctional nature of SA and the potential clinical impact of decreased SA are needed; in particular, the potential for certain treatments to reduce SA concentration, which may affect efficacy and toxicity of medications and disease progression., Competing Interests: DG, EL, and JVS are employees of argenx, the manufacturer of efgartigimod (FDA approved in gMG and under investigation in primary immune thrombocytopenia, pemphigus vulgaris and foliaceus, chronic inflammatory demyelinating polyneuropathy, bullous pemphigoid, and idiopathic inflammatory myopathy [myositis]). JTA has received funding from Syntimmune and argenx as part of fee-for-service agreements. ED is a postdoctoral research fellow of the Research Foundation – Flanders (grant number 12X9420N). JEK has participated on the Medical Advisory Committee of Sanofi Genzyme and Plasma Advisory Committee of Haemonetics. DR is the founder of Staten Biotechnology. NS is a member of the scientific advisory board and a speaker for argenx. IS, is supported by the Clinical Research Fund of the University Hospitals Leuven. ESW may receive royalties from patents owned by the UK Medical Research Council, UT Southwestern Medical Center, and Texas A&M University, and has financial interests in argenx, Astero BioPharma LLC, Astero Erado Inc., and Astero Technologies LLC. GV is a paid consultant for argenx. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The development (medical writing and editorial support) of this manuscript received funding from argenx. Authors who are not affiliated with argenx were not paid for their contributions to this work. The funder was involved in conception of design, interpretation of data, writing of this article, and decision to submit it for publication., (Copyright © 2022 Ward, Gelinas, Dreesen, Van Santbergen, Andersen, Silvestri, Kiss, Sleep, Rader, Kastelein, Louagie, Vidarsson and Spriet.)

Introduction: Limited evidence exists for healthcare resource utilization (HCRU) and costs associated with generalized myasthenia gravis (gMG), a rare autoimmune disorder, for adults in the United States., Methods: Adults with ≥1 diagnostic claim for MG between 2014 and 2019 were identified using Symphony Health's Integrated Dataverse®. Using a novel algorithm, HCRU and costs over 12 months following index dates were evaluated for patients with gMG including those with exacerbation events. For patients who experienced crisis events, HCRU and costs were analyzed during the 36 months preceding, during, and 12 months following the events., Results: Mean HCRU and costs were higher for newly diagnosed patients compared with previously diagnosed patients (hospitalizations: 0.46 vs. 0.34; all-cause costs: $26,419.20 vs. $24,941.47; direct costs for gMG treatments: $9,890.37 vs. $9,186.47) and further increased for patients with exacerbation events (hospitalizations: 0.72; all-cause costs: $43,734.15; direct costs for gMG treatments: $21,550.02). For patients who experienced crisis events, HCRU and costs markedly increased during the 12 months immediately before the crisis event (hospitalizations: 1.35; all-cause costs: $49,236.68) compared with the 2 preceding years and increased further during the 12 months following the crisis index date (hospitalizations: 2.78; all-cause costs: $173,956.99). Cost increases were, in large part, attributed to treatments received., Discussion: New diagnosis, exacerbation, and crisis events were drivers of HCRU and cost for patients with gMG. Particularly, high costs of gMG-specific medications associated with intervention for exacerbation and crisis events contributed to increased all-cause costs., Competing Interests: GP, DG, and EB are employees of argenx US Inc., Boston, MA, United States. YL is a paid consultant for and receives grant support from argenx US Inc., Boston, MA, United States. CA, AG, AW, and SB are employees of ZS Associates New York, NY, United States; Princeton, NJ, United States; Bangalore, India and serve as paid consultants for argenx US Inc., Boston, MA, United States., (Copyright © 2022 Phillips, Abreu, Goyal, Li, Whangbo, Gelinas, Brauer and Bhattacharya.)

Multiple quantitative trait loci for blood pressure (BP) are localized in humans and rodent models. Model studies have not only produced human quantitative trait loci homologues but also provided unforeseen mechanistic insights into the function modality of quantitative trait loci actions. Presently, congenic knockins, gene-specific knockout, and in vitro and in vivo function studies were used in a rat model of polygenic hypertension, DSS (Dahl salt sensitive) rats. One gene previously unknown in regulating BP was detected with 1 structural mutation(s) for each of 2 quantitative trait loci classified into 2 separate epistatic modules 1 and 3. C17QTL1 in epistatic module 2 was identified to be the gene Chrm3 encoding the M3R (muscarinic cholinergic 3 receptor), since a single function-enhancing M3R T556M conversion correlated with elevated BP. To definitively prove that the enhanced M3R function is responsible for BP changes by the DSS alleles of C17QTL1, we generated a Chrm3 gene-specific rat knockout. We observed a reduction in BP without tachycardia in both sexes, regardless of the amount of dietary salt, and an improvement in diastolic and kidney dysfunctions. All occurred in spite of a significant reduction in M3R-dependent vasodilation. The previously seen sexual dimorphism for C17QTL1 on BP disappeared in the absence of M3R. A Chrm3-coding variation increased M3R signaling, correlating with higher BP. Removing the M3R signaling led to a decrease in BP and improvements in cardiac and renal malfunctions. A novel pathogenic pathway accounted for a portion of polygenic hypertension and has implications in applying new diagnostic and therapeutic uses against hypertension and diastolic dysfunction.

Introduction: We explored adherence to the European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) guidelines for the diagnosis and treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) by reviewing data from a specialty pharmacy database., Materials and Methods: Clinical and electrophysiologic data were reviewed for 65 consecutive patients treated with intravenous immunoglobulin (IVIG) for CIDP. Three neuromuscular neurologists independently classified cases according to EFNS/PNS criteria as (1) fulfilling CIDP criteria; (2) non-CIDP (neither clinical nor electrophysiologic criteria met); or (3) unknown (insufficient information)., Results: Patients were treated by 31 different community neurologists in 14 states. Only seven patients (11%) met clinical and electrodiagnostic CIDP criteria. The remainder (89%) did not have CIDP (49%) or were unknown (40%). IVIG mean induction dose was 1.25 g/kg, mean maintenance dose 0.79 g/kg, and mean interval between infusions was 23 days., Conclusions: Adherence to EFNS/PNS CIDP diagnostic and treatment guidelines in the general neurologic community was poor. Improved education and awareness of widely available CIDP guidelines are recommended.

Alternative splicing is a key process underlying the evolution of increased proteomic and functional complexity and is especially prevalent in the mammalian nervous system. However, the factors and mechanisms governing nervous system-specific alternative splicing are not well understood. Through a genome-wide computational and expression profiling strategy, we have identified a tissue- and vertebrate-restricted Ser/Arg (SR) repeat splicing factor, the neural-specific SR-related protein of 100 kDa (nSR100). We show that nSR100 regulates an extensive network of brain-specific alternative exons enriched in genes that function in neural cell differentiation. nSR100 acts by increasing the levels of the neural/brain-enriched polypyrimidine tract binding protein and by interacting with its target transcripts. Disruption of nSR100 prevents neural cell differentiation in cell culture and in the developing zebrafish. Our results thus reveal a critical neural-specific alternative splicing regulator, the evolution of which has contributed to increased complexity in the vertebrate nervous system.

As an important embodiment of biomanipulation, injection of foreign materials (e.g., DNA, RNAi, sperm, protein, and drug compounds) into individual cells has significant implications in genetics, transgenics, assisted reproduction, and drug discovery. This paper presents a microrobotic system for fully automated zebrafish embryo injection, which overcomes the problems inherent in manual operation, such as human fatigue and large variations in success rates due to poor reproducibility. Based on computer vision and motion control, the microrobotic system performs injection at a speed of 15 zebrafish embryos (chorion unremoved) per minute, with a survival rate of 98% (n = 350 embryos), a success rate of 99% (n = 350 embryos), and a phenotypic rate of 98.5% (n = 210 embryos). The sample immobilization technique and microrobotic control method are applicable to other biological injection applications such as the injection of mouse oocytes/embryos and Drosophila embryos to enable high-throughput biological and pharmaceutical research.