Language of Lullabies: The Russification and De-Russification of the Baltic States

This article argues that the laws for promotion of the national languages are a legitimate means for the Baltic states to establish their cultural independence from Russia and the former Soviet Union

Febuxostat inhibition of endothelial-bound XO: Implications for targeting vascular ROS production

Xanthine oxidase (XO) is a critical source of reactive oxygen species (ROS) that contribute to vascular inflammation. Binding of XO to vascular endothelial cell glycosaminoglycans (GAGS) results in significant resistance to inhibition by traditional pyrazolopyrimidine-based inhibitors such as allopurinol. Therefore, we compared the extent of XO inhibition (free and GAG-bound) by allopurinol to that by febuxostat, a newly approved nonpurine XO-specific inhibitor. In solution, febuxostat was 1000-fold more potent than allopurinol at inhibiting XO-dependent uric acid formation (IC(50) = 1.8 nM vs 2.9 mu M). Association of XO with heparin-Sepharose 6B (HS6B-XO) had minimal effect on the inhibition of uric acid formation by febuxostat (IC(50) = 4.4 nM) while further limiting the effect of allopurinol (IC(50) = 64 mu M). Kinetic analysis of febuxostat inhibition revealed K(i) values of 0.96 (free) and 0.92 nM (HS6B-XO), confirming equivalent inhibition for both free and GAG-immobilized enzyme. When XO was bound to endothelial cell GAGs, complete enzyme inhibition was observed with 25 nM febuxostat, whereas no more than 80% inhibition was seen with either allopurinol or oxypurinol, even at concentrations above those tolerated clinically. The superior potency for inhibition of endothelium-associated XO is predictive of a significant role for febuxostat in investigating pathological states in which XO-derived ROS are contributive and traditional XO inhibitors are only slightly effective

Cardiovascular assessment tool for breast cancer survivors and oncology providers: Usability study

BACKGROUND: Cardiovascular health is of increasing concern to breast cancer survivors and their health care providers, as many survivors are more likely to die from cardiovascular disease than cancer. Implementing clinical decision support tools to address cardiovascular risk factor awareness in the oncology setting may enhance survivors\u27 attainment or maintenance of cardiovascular health. OBJECTIVE: We sought to evaluate survivors\u27 awareness of cardiovascular risk factors and examine the usability of a novel electronic health record enabled cardiovascular health tool from the perspective of both breast cancer survivors and oncology providers. METHODS: Breast cancer survivors (n=49) recruited from a survivorship clinic interacted with the cardiovascular health tool and completed pre and posttool assessments about cardiovascular health knowledge and perceptions of the tool. Oncologists, physician assistants, and nurse practitioners (n=20) who provide care to survivors also viewed the cardiovascular health tool and completed assessments of perceived usability and acceptability. RESULTS: Enrolled breast cancer survivors (84% White race, 4% Hispanic ethnicity) had been diagnosed 10.8 years ago (SD 6.0) with American Joint Committee on Cancer stage 0, I, or II (45/49, 92%). Prior to viewing the tool, 65% of survivors (32/49) reported not knowing their level for one or more cardiovascular health factors (range 0-4). On average, only 45% (range 0%-86%) of survivors\u27 known cardiovascular health factors were at an ideal level. More than 50% of survivors had ideal smoking status (45/48, 94%) or blood glucose level (29/45, 64%); meanwhile, less than 50% had ideal blood pressure (12/49, 24%), body mass index (12/49, 24%), cholesterol level (17/35, 49%), diet (7/49, 14%), and physical activity (10/49. 20%). More than 90% of survivors thought the tool was easy to understand (46/47, 98%), improved their understanding (43/47, 91%), and was helpful (45/47, 96%); overall, 94% (44/47 survivors) liked the tool. A majority of survivors (44/47, 94%) thought oncologists should discuss cardiovascular health during survivorship care. Most (12/20, 60%) oncology providers (female: 12/20, 60%; physicians: 14/20, 70%) had been practicing for more than 5 years. Most providers agreed the tool provided useful information (18/20, 90%), would help their effectiveness (18/20, 90%), was easy to use (20/20, 100%), and presented information in a useful format (19/20, 95%); and 85% of providers (17/20) reported they would use the tool most or all of the time when providing survivorship care. CONCLUSIONS: These usability data demonstrate acceptability of a cardiovascular health clinical decision support tool in oncology practices. Oncology providers and breast cancer survivors would likely value the integration of such apps in survivorship care. By increasing awareness and communication regarding cardiovascular health, electronic health record-enabled tools may improve survivorship care delivery for breast cancer and ultimately patient outcomes