Acute Hospital Outcomes for Renal Transplantation in Patients With Moderate or Severe Congenital Heart Disease.

Children and adults with congenital heart disease (CHD) are increasingly recognized to be at risk for acute and chronic renal injury. Some of these may progress to the need for renal transplantation. We hypothesized that patients with underlying moderate or severe CHD who undergo renal transplantation will have worse acute hospital outcomes. Using a national administrative database, we queried for admissions aged 0 to 50 years with moderate or severe CHD and renal transplantation and compared these to admissions without CHD. There were 56 admissions for renal transplantation in the CHD group (0.04%) and 26,285 admissions in the group without CHD (0.21%, p<0.001). The CHD group were younger, had a higher proportion of Whites, longer length of stay, higher complication rates, higher in-hospital mortality, and higher costs. In conclusion, although renal transplantation is still relatively uncommon in the CHD population, there is an increasing recognition of severe chronic renal disease in the setting of CHD, making it important to understand the potential implications of these findings.

Diné citizen science: Phytoremediation of uranium and arsenic in the Navajo Nation.

Mid-20th century mining in Naabeehó Bináhásdzo (Navajo Nation) polluted soil and groundwater with uranium and arsenic. The Diné and other indigenous residents of this region use groundwater for drinking, livestock, and irrigation, creating a serious environmental health risk. Currently, many individuals and communities on the Navajo Nation must purchase and transport treated water from hours away. Sunflowers (Helianthus annuus) preferentially take up uranium and arsenic, potentially representing a tool to remove these contaminants through on-site, low-cost phytoremediation. This study reports the results of a collaboration among researchers, high school students, teachers, and tribal leaders to analyze water chemistry and perform a phytoremediation experiment. In 2018 and 2019, we compiled existing data from the Navajo Nation Environmental Protection Agency (NNEPA) and collected samples from surface and groundwater. We then used sunflower seedlings grown in local soil to assess whether phytoremediation could be effective at removing arsenic and uranium. For the NNEPA-sampled wells, 9.5% exceeded the maximum contaminant level for uranium (30 µg per liter) and 16% for arsenic (10 µg per liter). For the new samples, uranium was highest in surface pools, suggesting leaching from local soil. Unlike studies from humid regions, sunflowers did not decrease uranium and arsenic in soil water. Instead, there was no change in arsenic concentration and an increase in uranium concentration in both planted and control treatments, attributable to weathering of uranium-bearing minerals in the desert soil. Because much of global uranium mining occurs in arid and semiarid regions, the ineffectiveness of phytoremediation on the Navajo Nation emphasizes the importance of prevention and conventional remediation. More generally, the participatory science approach created meaningful relationships and an important collaboration between a tribal chapter and a university, providing both cultural and scientific experiential learning opportunities for Diné high school students, undergraduate researchers, and senior personnel.

Synthesis and biological evaluation of novel pyrazolo[1,5-a]pyrimidines: Discovery of a selective inhibitor of JAK1 JH2 pseudokinase and VPS34.

A series of novel 3,6-di-substituted or 3-substituted pyrazolo[1,5-a]pyrimidines were prepared via a microwave-assisted approach that generated a broad array of derivatives in good yields (20-93%, ave. = 59%). The straightforward synthesis involved sequential treatment of commercially-available acetonitrile derivatives with DMF-dimethylacetal (120 °C, 20 min), followed by treatment with NH2NH2·HBr (120 °C, 20 min), and 1,1,3,3-tetramethoxypropane or 2-aryl-substituted malondialdehdyes (120 °C, 20 min). Compounds were screened for antimitotic activities against MCF7 breast cancer and/or A2780 ovarian cancer cell lines in vitro. The most active compounds exhibited EC50 values ranging from 0.5 to 4.3 µM, with the 3-(4-(trifluoromethyl)phenyl)-6-[4-(2-(piperidin-1-yl)ethoxy]phenyl analogue (34e) and the 3-(2-fluorophenyl)-6-[4-(2-(4-methylpiperizin-1-yl)ethoxy]phenyl analogue (35a) being two to three fold more active than Compound C (Dorsomorphin) in A2780 and MCF7 assays, respectively. Importantly, a monosubstituted 3-(benzothiazol-2-yl) derivative (13) was equipotent with the more synthetically challenging 3,6-disubstituted derivatives (34a-e and 35a-e), and exhibited a promising and unique selectivity profile when screened against a panel consisting of 403 protein kinases (Kinomescan™ selectivity score = 0.005, Kd = 0.55 ± 0.055 µM and 0.410 ± 0.20 µM for JAK1 JH2 pseudokinase and VPS34, respectively).