Impact of Tacrolimus Trough Variability on Acute Rejection Following Lung Transplantation.

BACKGROUND: Acute rejection is a risk factor for the development of chronic lung allograft dysfunction, the leading cause of morbidity and mortality in lung transplant recipients. Calcineurin inhibitors are the cornerstone of immunosuppression regimens after lung transplantation. METHODS: We retrospectively evaluated the association of tacrolimus level variability with total acute rejection score at 12 months post-transplant. Secondary outcomes included the development of chronic lung allograft dysfunction and antibody-mediated rejection at 24months post-transplant. There were 229 lung transplant recipients included. RESULTS: The mean (standard deviation) total rejection score of the cohort was 1.6 (1.7). Patients with high tacrolimus variability at 0 to 3, 3 to 6, and 6 to 12 months on average scored 0.18 (mean 1.6 vs 1.5; 95% CI): -0.3 to 0.66, P =.46), 0.14 (mean 1.7 vs 1.5; 95% CI: -0.32 to 0.6, P = .55), and 0.12 (mean 1.6 vs 1.5; 95% CI: -0.34 to 0.58, P = .62) point higher in 12-month total acute rejection scores, respectively; however, these differences were not statistically significant. The incidences of chronic lung allograft dysfunction and antibody-mediated rejection were numerically greater in the high variability group throughout certain periods; however, this was not consistent throughout all study timeframes and statistical significance was not evaluated. CONCLUSIONS: High tacrolimus variability was not associated with increased 12-month total acute rejection score. Further studies are needed to assess long-term outcomes with tacrolimus level variability.

Finding voices in the floods of Freedom Hill: innovating solutions in Princeville, North Carolina.

Princeville, NC, is the oldest town chartered by Blacks in America. Founded as Freedom Hill in 1865 and incorporated as Princeville in 1885, the town continues to be predominantly African American today. Built on the unwanted and flood-prone lands adjacent to the Tar River, Princeville has flooded multiple times throughout its history, including after Hurricane Floyd in 1999 and Hurricane Matthew in 2016. Because of the town's historical significance, residents and town officials alike have been reluctant to accept offers for widespread buyouts from the government. Despite having limited financial resources and political clout, the town has developed a unique approach to managed retreat while rebuilding from Matthew-one that emphasizes the importance of historical sites while also recognizing the need to relocate residents out of harm's way from future floods. This manuscript uses a historical and narrative approach to examine how Princeville's unique history, and the relationship between the town and the Tar River, play important roles in the town's decisions regarding retreat and redevelopment in the aftermath of major flooding events. We highlight the voices of current residents, including leaders, as well as the structural and cultural conditions that both constrain and enable the town's collective agency. While focused on the present day, this case study is historically informed, using oral histories and archival documents.

Multimodal Neurologic Enhancement Improves Preterm Infants' Developmental Outcomes: A Longitudinal Pilot Study.

PURPOSE: The purpose of this study was to identify the long-term developmental effects of a NICU music therapy intervention, Multimodal Neurologic Enhancement, provided to preterm infants in the NICU. DESIGN: Prospective randomized controlled study with one control group and one experimental group. SAMPLE: Participants were medically stable preterm infants with a birth age of 31 and 6/7 weeks or less, admitted to a level-III NICU. A total of 84 participants were enrolled, and 48 completed the study. MAIN OUTCOME VARIABLE: Post-discharge developmental scores on the Mullen Scales of Early Learning: AGS Edition. RESULTS: The experimental group performed significantly better than the control group on the Visual Reception and Early Learning Composite scores.

Structure-based virtual screening for novel inhibitors of the sarco/endoplasmic reticulum calcium ATPase and their experimental evaluation.

A public compound library with 260,000 compounds was screened virtually by computational docking for novel inhibitors of the transmembrane enzyme sarco/endoplasmic reticulum calcium ATPase (SERCA). Docking was performed with the program GOLD in conjunction with a high resolution X-ray crystal structure of SERCA. Compounds that were predicted to be active were tested in bioassays. Nineteen novel compounds were discovered that were capable of inhibiting the ATP hydrolysis activity of SERCA at concentrations below 50 microM. Crucial enzyme/inhibitor interactions were identified by analyzing the docking-predicted binding poses of active compounds. Like other SERCA inhibitors, the newly discovered compounds are of considerable medicinal interest because of their potential for cancer chemotherapy.