Physical Activity and Kidney Injury in Pediatric and Young Adult Kidney Transplant Recipients.

OBJECTIVES: To quantify physical activity and grip strength in pediatric kidney transplant recipients and describe attitudes about exercise and exercise counseling given concerns about allograft injury. STUDY DESIGN: This was a cross-sectional analysis of 101 kidney transplant recipients (7-21 years old) >6 months post-transplant. Patients completed the Physical Activity Questionnaire (PAQ). Grip strength was measured with a dynamometer. We asked about activity limitations and provider counseling. Univariate analysis and multiple linear regression were used to determine independent predictors of PAQ score and grip strength z score. RESULTS: We enrolled 101 of 122 eligible patients. Median PAQ score was 2.2 (range 0-5) and was lower compared with controls (P < .001). The average grip strength z score was -1.1 and -0.7 in the right and left hand, respectively. Predictors of lower grip strength were younger age (P = .036), non-African American race (P = .029), lower height z score (P = .010), and longer percentage of lifetime with kidney disease (P = .029). Although 49% and 67% limited exercise before and after transplant, respectively, 67% reported increased activity after transplant. By parent report, provider counseling included limiting certain activities (71%) and encouraging regular exercise (45%). CONCLUSION: Physical activity and grip strength are low after kidney transplant. Patients perceive an emphasis on exercise limitations rather than the benefits of regular exercise. Interventions that encourage physical activity may be beneficial.

Physician Workforce Diversity Is Still Necessary and Achievable if It Is Intentionally Prioritized.

The 2023 Supreme Court Decision from Students for Fair Admissions v. Harvard and Students for Fair Admissions v. University of North Carolina threatens the current progress in achieving diversity within undergraduate and graduate medical education. This is necessary to achieve a diverse healthcare workforce, which is a key to healing historical healthcare trauma, eliminating health disparities, and providing equitable healthcare access for all communities. Although the Supreme Court decision seems obstructionist, viable opportunities exist to enhance recruitment further and solidify diversity efforts in undergraduate and graduate medical education to achieve these goals.

Exchange transfusion safety and outcomes in neonatal hyperbilirubinemia.

OBJECTIVE: To characterize the prevalence of exchange transfusion (ET), clinical characteristics of infants receiving ET, and ET-associated morbidity and mortality. STUDY DESIGN: We conducted a multicenter cohort study of infants ≥23 weeks of gestational age (GA) with hyperbilirubinemia who underwent ET within 30 days of birth from 1997 to 2016. We examined clinical characteristics and adverse events after ET. We used multivariable logistic regression to examine the association between clinical risk factors and death. RESULT: A total of 1252 infants were included; 4% died within 7 days of ET and 6% died before discharge. Compared with infants ≥37 weeks of GA, infants ≤29 weeks of GA had greater odds of death (adjusted odds ratio [95% confidence interval] = 20.08 [7.32, 55.07]). CONCLUSIONS: Infants ≤ 29 weeks of GA had greater odds of death following ET compared with term infants. These data will support clinicians in evaluating risks and prognosis for infants who require ET.

Trends and Racial and Geographic Differences in Infant Mortality in the United States Due to Necrotizing Enterocolitis, 1999 to 2020.

This cohort study analyzes yearly trends in necrotizing enterocolitis­related infant mortality rates (NEC-IMR) from 1999 to 2020, overall and by Black and White race, and described Black-to-White NEC-IMR ratios and NEC-IMR for US states.

Proinflammatory cytokine-induced tight junction remodeling through dynamic self-assembly of claudins.

Tight junctions (TJs) are dynamic, multiprotein intercellular adhesive contacts that provide a vital barrier function in epithelial tissues. TJs are remodeled during physiological development and pathological mucosal inflammation, and differential expression of the claudin family of TJ proteins determines epithelial barrier properties. However, the molecular mechanisms involved in TJ remodeling are incompletely understood. Using acGFP-claudin 4 as a biosensor of TJ remodeling, we observed increased claudin 4 fluorescence recovery after photobleaching (FRAP) dynamics in response to inflammatory cytokines. Interferon γ and tumor necrosis factor α increased the proportion of mobile claudin 4 in the TJ. Up-regulation of claudin 4 protein rescued these mobility defects and cytokine-induced barrier compromise. Furthermore, claudins 2 and 4 have reciprocal effects on epithelial barrier function, exhibit differential FRAP dynamics, and compete for residency within the TJ. These findings establish a model of TJs as self-assembling systems that undergo remodeling in response to proinflammatory cytokines through a mechanism of heterotypic claudin-binding incompatibility.

Trans-dimerization of JAM-A regulates Rap2 and is mediated by a domain that is distinct from the cis-dimerization interface.

Junctional adhesion molecule-A (JAM-A) is a tight junction-associated signaling protein that regulates epithelial cell proliferation, migration, and barrier function. JAM-A dimerization on a common cell surface (in cis) has been shown to regulate cell migration, and evidence suggests that JAM-A may form homodimers between cells (in trans). Indeed, transfection experiments revealed accumulation of JAM-A at sites between transfected cells, which was lost in cells expressing cis- or predicted trans-dimerization null mutants. Of importance, microspheres coated with JAM-A containing alanine substitutions to residues 43NNP45 (NNP-JAM-A) within the predicted trans-dimerization site did not aggregate. In contrast, beads coated with cis-null JAM-A demonstrated enhanced clustering similar to that observed with wild-type (WT) JAM-A. In addition, atomic force microscopy revealed decreased association forces in NNP-JAM-A compared with WT and cis-null JAM-A. Assessment of effects of JAM-A dimerization on cell signaling revealed that expression of trans- but not cis-null JAM-A mutants decreased Rap2 activity. Furthermore, confluent cells, which enable trans-dimerization, had enhanced Rap2 activity. Taken together, these results suggest that trans-dimerization of JAM-A occurs at a unique site and with different affinity compared with dimerization in cis. Trans-dimerization of JAM-A may thus act as a barrier-inducing molecular switch that is activated when cells become confluent.