This study provides Class IV evidence that for patients with anti-MuSK MG, rituximab increased the probability of a favorable outcome.

Introduction: A randomized trial demonstrated benefit from thymectomy in nonthymomatous acetylcholine receptor (AChR)‐antibody positive myasthenia gravis (MG). Uncontrolled observational and histologic studies suggest thymectomy may not be efficacious in anti–muscle‐specific kinase (MuSK)‐MG. Methods: The therapeutic impact of thymectomy was evaluated from data collected for a multicenter, retrospective blinded review of rituximab in MuSK‐MG. Results: Baseline characteristics were similar between thymectomy (n = 26) and nonthymectomy (n = 29) groups, including treatment with rituximab (42% vs. 45%). At last visit, 35% of thymectomy subjects reached the primary endpoint, a Myasthenia Gravis Foundation of America (MGFA) post‐intervention status (PIS) score of minimal manifestations (MM) or better, compared with 55% of controls (P = 0.17). After controlling for age at onset of MG, rituximab, prednisone, and intravenous immunoglobulin/plasma exchange treatment, thymectomy was not associated with greater likelihood of favorable clinical outcome (odds ratio = 0.43, 95% confidence interval 0.12–1.53, P = 0.19). Discussion: Thymectomy was not associated with additional clinical improvement in this multicenter cohort of MuSK‐MG patients. Muscle Nerve 59:404–410, 2019

Edited by Jeffrey E. PessinAlthough it is well-established how nutrients, growth factors, and hormones impact functional ␤-cell mass (BCM), the influence of the central nervous system in this regard, and especially in the context of islet immune modulation, has been understudied. Here we investigated the expression and activity of pancreatic islet ␣7 nicotinic acetylcholine receptor (␣7nAChR) in islet anti-inflammatory and prosurvival signaling. Systemic administration of ␣7nAChR agonists in mice improved glucose tolerance and curtailed streptozotocin-induced hyperglycemia by retaining BCM, in part through maintaining Pdx1 and MafA expression and reducing apoptosis. ␣7nAChR activation of mouse islets ex vivo led to reduced inflammatory drive through a JAK2-STAT3 pathway that couples with CREB/Irs2/Akt survival signaling. Because the vagus nerve conveys anti-inflammatory signals to immune cells of the spleen and other nonneural tissues in the viscera by activating ␣7nAChR agonists, our study suggests a novel role for ␤-cell ␣7nAChR that functions to maintain ␤-cell survival and mass homeostasis through modulating islet cytokine and phosphatidylinositol 3-kinase-dependent signaling pathways. Exploiting these pathways may have therapeutic potential for the treatment of autoimmune diabetes. element-binding protein.; Veh, vehicle; i.p., intraperitoneal; IPGTT, intraperitoneal glucose tolerance test; TUNEL, deoxynucleotidyltransferase-mediated dUTP nick end labeling. Reagents for ␣7nAChR manipulationThe partial agonist GTS-21 (Tocris Bioscience) and the specific agonist PNU-282987 (Alomone Labs) were used for ␣7R activation, whereas MLA (Tocris) was used as a specific ␣7R ␣7nAChR agonists preserve ␤-cell mass

Enzymatic cleavage of Amyloid-β Protein Precursor (AβPP) produces amyloid-β (Aβ) peptides which form the insoluble cortical plaques characteristic of Alzheimer’s Disease (AD). AβPP is post-transcriptionally processed into three major isoforms with differential cellular and tissue expression patterns. Changes in AβPP isoform expression may be indicative of disease pathogenesis in AD, but accurately measuring AβPP gene isoforms has been difficult to standardize, reproduce, and interpret. In light of this, we developed a set of isoform specific absolute quantification real time PCR standards that allow for quantification of transcript copy numbers for total AβPP and all three major isoforms (AβPP695, AβPP751, and AβPP770) in addition to glyceraldehyde-3-dehydrogenase (GAPDH) and examined expression patterns in superior frontal gyrus (SFG) and cerebellar (CBL) samples from patients with (n=12) and without AD (n=10). Both total AβPP and AβPP695 transcripts were significantly decreased in superior frontal gyrus (SFG) of patients with AD compared to control (p= 0.037 and p=0.034, respectively). AβPP751 and AβPP770 transcripts numbers were not significantly different between AD and control (p>0.15). There was trend for decreased percentage AβPP695 (p=0.051) and increased percentage AβPP770 (p=0.013) expression in SFG of patients with AD. GAPDH transcripts levels were also decreased significantly in the SFG of patients with AD compared to control (p=0.005). Decreasing Total AβPP and AβPP695 copy number was associated with increased plaque burden and decreased cognitive function. In this study we describe a simple procedure for measuring AβPP isoform transcripts by real-time PCR and confirm previous studies showing altered AβPP isoform expression patterns in AD.