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Cardiotoxicity is a major complication of anthracycline therapy that negatively impacts prognosis. Effective pharmacotherapies for prevention of anthracycline-induced cardiomyopathy (AICM) are currently lacking. Increased plasma levels of the neutrophil-derived enzyme myeloperoxidase (MPO) predict occurrence of AICM in humans. We hypothesized that MPO release causally contributes to AICM. Mice intravenously injected with the anthracycline doxorubicin (DOX) exhibited higher neutrophil counts and MPO levels in the circulation and cardiac tissue compared to saline (NaCl)-treated controls. Neutrophil-like HL-60 cells exhibited increased MPO release upon exposition to DOX. DOX induced extensive nitrosative stress in cardiac tissue alongside with increased carbonylation of sarcomeric proteins in wildtype but not in Mpo−/− mice. Accordingly, co-treatment of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) with DOX and MPO aggravated loss of hiPSC-CM-contractility compared to DOX treatment alone. DOX-treated animals exhibited pronounced cardiac apoptosis and inflammation, which was attenuated in MPO-deficient animals. Finally, genetic MPO deficiency and pharmacological MPO inhibition protected mice from the development of AICM. The anticancer efficacy of DOX was unaffected by MPO deficiency. Herein we identify MPO as a critical mediator of AICM. We demonstrate that DOX induces cardiac neutrophil infiltration and release of MPO, which directly impairs cardiac contractility through promoting oxidation of sarcomeric proteins, cardiac inflammation and cardiomyocyte apoptosis. MPO thus emerges as a promising pharmacological target for prevention of AICM. [ABSTRACT FROM AUTHOR]

Background: Canine lymphoma is one of the most frequently occurring malignant neoplasms in dogs. Anthracycline-based chemotherapy for the treatment of canine lymphoma is very effective; however, there is not enough evidence for the development of cardiac toxicity using several anthracyclines as chemotherapeutic agents. Case Description: An 8-year-old, castrated, mixed-breed dog was diagnosed with multicentric lymphoma and received multi-agent chemotherapy. Complete remission was achieved, but the patient had a relapse of lymphoma. After third-line chemotherapy with epirubicin, the patient was diagnosed with dilated cardiomyopathy. The total cumulative doses of doxorubicin, mitoxantrone, and epirubicin were 125, 8, and 125 mg/m2, respectively. Although the patient was treated with cardiac drugs and clinically stabilized, the patient had a relapse of lymphoma and died shortly after the diagnosis of cardiomyopathy. Conclusion: The patient was suspected to have anthracycline-induced cardiomyopathy. Further studies are required to establish prevention and management strategies for dogs receiving potentially cardiotoxic therapies such as anthracyclines.

Single-transect methods of shoreline change prediction are unparsimonious, i.e., they tend to overfit data by using more parameters than necessary because they assume that both signal and noise at adjacent transects are independent. Here we introduce some new methods that reduce overfitting by expressing change rate as a linear sum of basis functions. In the method of IC-binning, the basis functions are boxcars-an information criterion is used to assign contiguous alongshore locations into bins within which change rate is constant; the resulting rate is discontinuous but may be useful for beach management. In the polynomial method, the basis functions are polynomials in alongshore distance, and the change rate varies continuously along the beach. In the eigenbeaches method, the basis functions are the principal components of the matrix of shorelines. To choose the number of basis functions in each method, and to compare methods with each other, we use an information criterion. We apply these new methods to shoreline change on Maui Island, Hawaii, briefly here, and in more detail in a companion paper. The polynomial method works best for short beaches with rates that vary slowly in the alongshore direction while eigenbeaches works best for shorelines that are long, or have rates that vary rapidly in the alongshore direction. The Schwarz information criterion and the AICu version of the Akaike information criterion performed well in tests on real data and noisy synthetic data. [ABSTRACT FROM AUTHOR]

Background: Canine lymphoma is one of the most frequently occurring malignant neoplasms in dogs. Anthracycline-based chemotherapy for the treatment of canine lymphoma is very effective; however, there is not enough evidence for the development of cardiac toxicity using several anthracyclines as chemotherapeutic agents., Case Description: An 8-year-old, castrated, mixed-breed dog was diagnosed with multicentric lymphoma and received multi-agent chemotherapy. Complete remission was achieved, but the patient had a relapse of lymphoma. After third-line chemotherapy with epirubicin, the patient was diagnosed with dilated cardiomyopathy. The total cumulative doses of doxorubicin, mitoxantrone, and epirubicin were 125, 8, and 125 mg/m 2 , respectively. Although the patient was treated with cardiac drugs and clinically stabilized, the patient had a relapse of lymphoma and died shortly after the diagnosis of cardiomyopathy., Conclusion: The patient was suspected to have anthracycline-induced cardiomyopathy. Further studies are required to establish prevention and management strategies for dogs receiving potentially cardiotoxic therapies, such as anthracyclines., Competing Interests: The authors declare that there is no conflict of interest.