adults and adolescents are insufficiently active. Physical activity fosters normal growth and development and can make people feel, function, and sleep better and reduce risk of many chronic diseases.OBJECTIVE To summarize key guidelines in the Physical Activity Guidelines for Americans, 2nd edition (PAG). PROCESS AND EVIDENCE SYNTHESISThe 2018 Physical Activity Guidelines Advisory Committee conducted a systematic review of the science supporting physical activity and health. The committee addressed 38 questions and 104 subquestions and graded the evidence based on consistency and quality of the research. Evidence graded as strong or moderate was the basis of the key guidelines. The Department of Health and Human Services (HHS) based the PAG on the 2018 Physical Activity Guidelines Advisory Committee Scientific Report. RECOMMENDATIONSThe PAG provides information and guidance on the types and amounts of physical activity to improve a variety of health outcomes for multiple population groups. Preschool-aged children (3 through 5 years) should be physically active throughout the day to enhance growth and development. Children and adolescents aged 6 through 17 years should do 60 minutes or more of moderate-to-vigorous physical activity daily. Adults should do at least 150 minutes to 300 minutes a week of moderate-intensity, or 75 minutes to 150 minutes a week of vigorous-intensity aerobic physical activity, or an equivalent combination of moderate-and vigorous-intensity aerobic activity. They should also do muscle-strengthening activities on 2 or more days a week. Older adults should do multicomponent physical activity that includes balance training as well as aerobic and muscle-strengthening activities. Pregnant and postpartum women should do at least 150 minutes of moderate-intensity aerobic activity a week. Adults with chronic conditions or disabilities, who are able, should follow the key guidelines for adults and do both aerobic and muscle-strengthening activities. Recommendations emphasize that moving more and sitting less will benefit nearly everyone. Individuals performing the least physical activity benefit most by even modest increases in moderate-to-vigorous physical activity. Additional benefits occur with more physical activity. Both aerobic and muscle-strengthening physical activity are beneficial. CONCLUSIONS AND RELEVANCEThe Physical Activity Guidelines for Americans, 2nd edition, provides information and guidance on the types and amounts of physical activity that provide substantial health benefits. Health professionals and policy makers should facilitate awareness of the guidelines and promote the health benefits of physical activity and support efforts to implement programs, practices, and policies to facilitate increased physical activity and to improve the health of the US population.

Anthracyclines, such as doxorubicin and daunorubicin, are highly effective anticancer agents that produce a well-described but incompletely understood cardiac toxicity. According to a popular hypothesis, anthracyclines injure the heart by generating oxygen-centered free radicals. This free radical hypothesis, however, appears to be inconsistent with many observations, such as the frequent failure of anthracyclines at cardiotoxic doses to produce evidence of increased free radical generation. Other explanations of cardiotoxicity involve platelet-activating factor, prostaglandins, histamine, calcium, and C-13 hydroxy anthracycline metabolites. These C-13 hydroxy metabolites, on the basis of in vitro data, are considerably more potent than parent compounds as myocardial depressants and as inhibitors of ATPases of sarcoplasmic reticulum, mitochondria, and sarcolemma. Further studies will be required to determine whether metabolites or the other putative injurious agents discussed contribute substantially to the cardiomyopathy of anthracycline therapy. The hypotheses presented in this paper should provide a useful framework for subsequent investigations into the mechanisms of anthracycline cardiotoxicity.

Doxorubicin (former generic name, adriamycin), a highly effective anticancer drug, produces cardiotoxicity, which limits its therapeutic potential. The mechanism of this cardiotoxicity has remained elusive. Our data suggest that this toxicity could involve doxorubicinol, the primary circulating metabolite of doxorubicin. Doxorubicinol was markedly more potent than doxorubicin at compromising both systolic and diastolic cardiac function. Similarly, doxorubicinol was much more potent than doxorubicin at inhibiting the calcium pump of sarcoplasmic reticulum [ATP phosphohydrolase (Ca2+-transporting), EC 3.6

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Purpose: To review and update the evidence of the relationship between physical activity, risk of fall-related injury, and physical function in community-dwelling older people that was presented in the 2018 Physical Activity Guidelines Advisory Committee Scientific Report (PAGAC Report). Methods: Duplicate independent screenings of 1,415 systematic reviews and meta-analyses published between 2006 and 2016 identified from PubMed®, Cochrane Library, and CINAHL databases yielded 111 articles used for the PAGAC Report. The PAGAC Aging Subcommittee members graded scientific evidence strength based upon a 5-criteria rubric and assigned one of four grades: strong, moderate, limited, or not assignable. An updated search of 368 articles published between January 2017 and March 2018 yielded 35 additional pertinent articles.

Subclinical leaflet thrombosis was recently described in a randomized trial of transcatheter aortic valve replacement. It was subsequently demonstrated in a series of registries that this was a commonly observed imaging finding seen in all transcatheter and surgical bioprostheses. The phenomenon has aroused considerable interest due to the as-yet-undefined risk for later clinical events and the possibility of pharmacological intervention with anticoagulation. Subclinical leaflet thrombosis is easily detected noninvasively by technically suitable computed tomography (CT) with a high degree of concordance to transesophageal echocardiography findings. The CT hallmarks were noted to be hypoattenuated leaflet thickening (HALT) associated with reduced leaflet motion (RELM). The combination of HALT and RELM signified hypoattenuation affecting motion, the standardized imaging endpoint used. This paper describes the systematic CT evaluation methodology that was devised during the Portico trial investigation and U.S. Food and Drug Administration submission; it also highlights the need for an ongoing discussion among experts to enable, with the help of the Valve Academic Research Consortium, standardization of reporting of this imaging finding to cater to the present and future needs of clinical trials.

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