Normal placental development and angiogenesis are crucial for fetal growth and maternal health during pregnancy. However, molecular regulation of placental angiogenesis has been difficult to study due to a lack of specific genetic tools that isolate the placenta from the embryo and yolk sac. To address this gap in knowledge we recently developed mice in which Cre is expressed in allantois-derived cells, including placental endothelial and stromal cells.
View Article and Find Full Text PDFThere is a strong and growing focus on self-determination in French-speaking countries, and this pilot study reports the technical adequacy of the Self-Determination Inventory: Student Report (SDI:SR) French Translation. Data were collected with 471 French-speaking youth with and without disabilities in Canada (Quebec), Switzerland, France, and Belgium. Key findings showed it was feasible to use 20 (of 21) items to represent the self-determination construct in the French-speaking sample.
View Article and Find Full Text PDFPodocytes and parietal epithelial cells (PECs) are among the few principal cell types within the kidney glomerulus, the former serving as a crucial constituent of the kidney filtration barrier and the latter representing a supporting epithelial layer that adorns the inner wall of Bowman's capsule. Podocytes and PECs share a circumscript developmental lineage that only begins to diverge during the S-shaped body stage of nephron formation-occurring immediately before the emergence of the fully mature nephron. These two cell types, therefore, share a highly conserved gene expression program, evidenced by recently discovered intermediate cell types occupying a distinct spatiotemporal gene expression zone between podocytes and PECs.
View Article and Find Full Text PDFResearch literature and community narratives both emphasize the importance of self-determination in the lives of deaf youth. This paper describes the development, initial validation, and potential applications of a translated measure of self-determination for deaf youth, the SDI:SR ASL Translation (SDI:SR ASL). A sample of 3,309 young people who completed the SDI:SR, of whom 392 were deaf, was used in this validation study.
View Article and Find Full Text PDFWe model pass/fail examinations aiming to provide a systematic tool to minimize classification errors. We use the method of cut-score operating functions to generate specific cut-scores on the basis of minimizing several important misclassification measures. The goal of this research is to examine the combined effects of a known distribution of examinee abilities and uncertainty in the standard setting on the optimal choice of the cut-score.
View Article and Find Full Text PDFPodocyte loss triggering aberrant activation and proliferation of parietal epithelial cells (PECs) is a central pathogenic event in proliferative glomerulopathies. Podocyte-specific Krüppel-like factor 4 (KLF4), a zinc-finger transcription factor, is essential for maintaining podocyte homeostasis and PEC quiescence. Using mice with podocyte-specific knockdown of Klf4, we conducted glomerular RNA-sequencing, tandem mass spectrometry, and single-nucleus RNA-sequencing to identify cell-specific transcriptional changes that trigger PEC activation due to podocyte loss.
View Article and Find Full Text PDFThe Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway is a multifaceted transduction system that regulates cellular responses to incoming signaling ligands. STAT3 is a central member of the JAK/STAT signaling cascade and has long been recognized for its increased transcriptional activity in cancers and autoimmune disorders but has only recently been in the spotlight for its role in the progression of kidney disease. Although genetic knockout and manipulation studies have demonstrated the salutary benefits of inhibiting STAT3 activity in several kidney disease models, pharmacological inhibition has yet to make it to the clinical forefront.
View Article and Find Full Text PDFBackground: Podocyte injury is the hallmark of proteinuric kidney diseases, such as FSGS and minimal change disease, and destabilization of the podocyte's actin cytoskeleton contributes to podocyte dysfunction in many of these conditions. Although agents, such as glucocorticoids and cyclosporin, stabilize the actin cytoskeleton, systemic toxicity hinders chronic use. We previously showed that loss of the kidney-enriched zinc finger transcription factor Krüppel-like factor 15 (KLF15) increases susceptibility to proteinuric kidney disease and attenuates the salutary effects of retinoic acid and glucocorticoids in the podocyte.
View Article and Find Full Text PDFPathologic glomerular epithelial cell (GEC) hyperplasia is characteristic of both rapidly progressive glomerulonephritis (RPGN) and subtypes of focal segmental glomerulosclerosis (FSGS). Although initial podocyte injury resulting in activation of STAT3 signals GEC proliferation in both diseases, mechanisms regulating this are unknown. Here, we show that the loss of Krüppel-like factor 4 (KLF4), a zinc-finger transcription factor, enhances GEC proliferation in both RPGN and FSGS due to dysregulated STAT3 signaling.
View Article and Find Full Text PDFJ Pediatr Gastroenterol Nutr
March 2018
Objectives: Infants with short bowel syndrome (SBS) require diligent nutritional support for adequate growth. Enteral independence is a primary goal, but must be balanced with ensuring sufficient nutrition. We aimed to describe growth trajectory in infants with SBS as function of nutritional intake during first 2 years of life.
View Article and Find Full Text PDFLarge epidemiological studies clearly demonstrate that multiple episodes of acute kidney injury contribute to the development and progression of kidney fibrosis. Although our understanding of kidney fibrosis has improved in the past two decades, we have limited therapeutic strategies to halt its progression. Myofibroblast differentiation and proliferation remain critical to the progression of kidney fibrosis.
View Article and Find Full Text PDFBackground And Objectives: Cystic fibrosis (CF) is known for its impact on the lung and pancreas of individuals; however, impaired growth is also a common complication. We hypothesized that targeting the biological defect in the CF transmembrane conductance regulator (CFTR) protein may affect growth outcomes.
Methods: In this post hoc analysis, we assessed linear growth and weight in 83 children (aged 6-11 years) enrolled in 2 clinical trials, the longitudinal-observation GOAL study and the placebo-controlled ENVISION study, to evaluate the effects of ivacaftor, a CFTR potentiator.
We used integrated and conjoint confirmatory factor analysis of Shipley-2 and Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV) data to investigate constructs measured in the Shipley-2 for children and adolescents. We also estimated Shipley-2 composite reliability at the subtest level rather than the item level. The three Shipley-2 subtests for the most part measured what was described in the manual, although Block Patterns measured visual spatial ability in addition to fluid ability and Abstraction was best considered a measure of psychometric g.
View Article and Find Full Text PDFBackground: Advocates of medial portal drilling claim that the transtibial technique results in a more vertical positioning of the graft, which could lead to subsequent failure and/or a residual pivot shift on postoperative examination. However, advocates of transtibial drilling state that with appropriate placement and adequate notchplasty, their technique places the graft in a more anatomically correct position on the wall, negating the resultant potential for pivot shift and early postoperative failure.
Hypothesis: Transtibial femoral drilling can adequately reproduce the femoral origin of the anterior cruciate ligament (ACL) and place the graft in an anatomical position equivalent to medial portal drilling.