The mERG1a channel modulates skeletal muscle MuRF1, but not MAFbx, expression.

INTRODUCTION: We investigated the mechanism by which the MERG1a K+ channel increases ubiquitin proteasome proteolysis (UPP). METHODS: Hindlimb suspension and electro-transfer of Merg1a cDNA into mouse gastrocnemius muscles induced atrophy. RESULTS: Atrophic gastrocnemius muscles of hindlimb-suspended mice express Merg1a, Murf1, and Mafbx genes. Electrotransfer of Merg1a significantly decreases muscle fiber size (12.6%) and increases UPP E3 ligase Murf1 mRNA (2.1-fold) and protein (23.7%), but does not affect Mafbx E3 ligase expression. Neither Merg1a-induced decreased fiber size nor Merg1a-induced increased Murf1 expression is curtailed significantly by coexpression of inactive HR-Foxo3a, a gene encoding a transcription factor known to induce Mafbx expression. CONCLUSIONS: The MERG1a K+ channel significantly increases expression of Murf1, but not Mafbx. We explored this expression pattern by expressing inactive Foxo3a and showing that it is not involved in MERG1a-mediated expression of Murf1. These findings suggest that MERG1a may not modulate Murf1 expression through the AKT/FOXO pathway.

Pharmacoeconomic Analysis of Heartworm Preventive Compliance and Revenue in Veterinary Practices in the United States.

Background: Heartworm disease (HWD) is a potentially fatal condition caused by the nematode Dirofilaria immitis. It is endemic in North America, and the American Heartworm Society recommends that owned dogs be on a Food and Drug Administration-approved HWD preventive year-round. The objective of this study was to compare the 12-month HWD preventive purchase compliance rates of injectable moxidectin (ProHeart® 6) and the dose equivalent in monthly HWD preventives and their associated economic value to the veterinary hospital. Methods: This study used retrospective anonymized transactional data of 7,926,392 unique dogs from 3,737 companion animal practices across the US for the period 2014-2017. Compliance was defined using American Heartworm Society guidelines. Comparisons were purchases of a 6-month moxidectin injection or six doses of any monthly HWD or HWD combination preventive product, tracked for the next preventive purchase 5-7 months later. Total revenue, HWD prevention cost, 12-month repurchase compliance, and patient retention were calculated. Data were expressed on an annualized basis. Compliance comparisons were calculated based on proportion analysis with the SAS ProbNorm function (SAS 9.4, Cary, NC), using a two-sided t-test, at the 5% level of significance (P < 0.05). Results: At 51.7%, annual compliance with injectable moxidectin was higher than the dose equivalent in monthly HWD preventives, which was 24.4% (P = 0.0001). Eighty-five percent of patients on injectable moxidectin recorded additional transactions during the first visit (average invoice of $161), compared with only 55% of pet owners who purchased monthly HWD prevention (average invoice $141) or monthly HWD combination (average invoice of $171). The average costs of 6 months of HWD preventives were as follows: injectable moxidectin, $48 (29.7% of the total visit invoice); monthly HWD prevention, $45 (31.0% of the total invoice); and monthly HWD combination, 95 (55.6% of the total visit invoice). Finally, dogs receiving injectable moxidectin had a higher proportion of patients with repeat injections within 12 months between 2014 and 2017, with 68% retention rate after 4 years. In comparison, the six-dose monthly HWD cohort retention rate dropped to 55% by 2017. Conclusions: Dogs receiving injectable moxidectin had higher HWD preventive compliance, generated more practice revenue, and had a higher rate of practice retention compared with monthly HWD products.