Enhanced chondrogenesis and Wnt signaling in PTH-treated fractures.

Studies have shown that systemic PTH treatment enhanced the rate of bone repair in rodent models. However, the mechanisms through which PTH affects bone repair have not been elucidated. In these studies we show that PTH primarily enhanced the earliest stages of endochondral bone repair by increasing chondrocyte recruitment and rate of differentiation. In coordination with these cellular events, we observed an increased level of canonical Wnt-signaling in PTH-treated bones at multiple time-points across the time-course of fracture repair, supporting the conclusion that PTH responses are at least in part mediated through Wnt signaling. INTRODUCTION: Since FDA approval of PTH [PTH(1-34); Forteo] as a treatment for osteoporosis, there has been interest in its use in other musculoskeletal conditions. Fracture repair is one area in which PTH may have a significant clinical impact. Multiple animal studies have shown that systemic PTH treatment of healing fractures increased both callus volume and return of mechanical competence in models of fracture healing. Whereas the potential for PTH has been established, the mechanism(s) by which PTH produces these effects remain elusive. MATERIALS AND METHODS: Closed femoral fractures were generated in 8-wk-old male C57Bl/6 mice followed by daily systemic injections of either saline (control) or 30 microg/kg PTH(1-34) for 14 days after fracture. Bones were harvested at days 2, 3, 5, 7, 10, 14, 21, and 28 after fracture and analyzed at the tissue level by radiography and histomorphometry and at the molecular and biochemical levels level by RNase protection assay (RPA), real-time PCR, and Western blot analysis. RESULTS: Quantitative muCT analysis showed that PTH treatment induced a larger callus cross-sectional area, length, and total volume compared with controls. Molecular analysis of the expression of extracellular matrix genes associated with chondrogenesis and osteogenesis showed that PTH treated fractures displayed a 3-fold greater increase in chondrogenesis relative to osteogenesis over the course of the repair process. In addition, chondrocyte hypertrophy occurred earlier in the PTH-treated callus tissues. Analysis of the expression of potential mediators of PTH actions showed that PTH treatment significantly induced the expression of Wnts 4, 5a, 5b, and 10b and increased levels of unphosphorylated, nuclear localized beta-catenin protein, a central feature of canonical Wnt signaling. CONCLUSIONS: These results showed that the PTH-mediated enhancement of fracture repair is primarily associated with an amplification of chondrocyte recruitment and maturation in the early fracture callus. Associated with these cellular effects, we observed an increase in canonical Wnt signaling supporting the conclusion that PTH effects on bone repair are mediated at least in part through the activation of Wnt-signaling pathways.     

The Turner syndrome research registry: Creating equipoise between investigators and participants

To address knowledge gaps about Turner syndrome (TS) associated disease mechanisms, the Turner Syndrome Society of the United States created the Turner Syndrome Research Registry (TSRR), a patient‐powered registry for girls and women with TS. More than 600 participants, parents or guardians completed a 33‐item foundational survey that included questions about demographics, medical conditions, psychological conditions, sexuality, hormonal therapy, patient and provider knowledge about TS, and patient satisfaction. The TSRR platform is engineered to allow individuals living with rare conditions and investigators to work side‐by‐side. The purpose of this article is to introduce the concept, architecture, and currently available content of the TSRR, in anticipation of inviting proposals to utilize registry resources.     

The impact of somatic mosaicism on bicuspid aortic valve and aortic dissection in Turner Syndrome

Somatic mosaicism is a major modifier of turner syndrome (TS) features and may be more prevalent than once thought, as new molecular techniques enable detection of tissue‐specific mosaicism. This review explores the causes of mosaicism, discusses how mosaicism may impact congenital aortic defects in TS, and summarizes molecular methods to detect mosaicism in different contexts.     

Social–Emotional Profiles of PTSD,Complex PTSD,and Borderline Personality Disorder Among Racially and Ethnically Diverse Young Adults: A Latent Class Analysis

The debate around the construct validity of complex posttraumatic stress disorder (CPTSD) has begun to examine whether CPTSD diverges from posttraumatic stress disorder (PTSD) when it co‐occurs with the diagnosis of borderline personality disorder (BPD). The present study (a) examined the construct validity of CPTSD through a latent class analysis of a non–treatment‐seeking sample of young trauma‐exposed adults and (b) characterized each class in terms of trauma characteristics, social emotions (e.g., shame, guilt, blame), and interpersonal functioning. A total of 23 dichotomized survey items were chosen to represent the symptoms of PTSD, CPTSD, and BPD and administered to 197 trauma‐exposed participants. Fit statistics compared models with 2–4 latent classes. The four‐class model showed the best fit statistics and clinical interpretability. Classes included a “high PTSD+CPTSD+BPD” class, characterized by high‐level endorsement of all symptoms for the three diagnoses; a “moderate PTSD+CPTSD+BPD” class, characterized by endorsement of some symptoms across all three diagnoses; a “PTSD” class, characterized by endorsement of the ICD‐11 PTSD criteria; and a “healthy” class, characterized by low symptom endorsement overall. Pairwise comparisons showed individuals in the high PTSD+CPTSD+BPD class to have the highest levels of psychological distress, traumatic event history, adverse childhood experiences, and PTSD symptoms. Shame was the only social emotion to significantly differ between the classes, p = .002, η² = .16. The findings diverge from the literature, indicating an overlap of PTSD, CPTSD, and BPD symptoms in a non–treatment‐seeking community sample. Further, shame may be a central emotion that differentiates between presentation severities following trauma exposure.     

Estimates of the annual number of clinically recognized pregnancies in the United States, 1981-1991.

The authors estimated the number of clinically recognized pregnancies that occurred annually from 1981 to 1991 in the United States by type of outcome and by race. Estimates of the numbers of livebirths, induced abortions, ectopic pregnancies, and fetal deaths were obtained by using data from the Centers for Disease Control and Prevention in Atlanta, Georgia. The number of spontaneous abortions was estimated by using previously published, age-specific rates. More than 67 million pregnancies occurred during the study period. Overall, 62.5% of these pregnancies resulted in livebirths, 21.9% in legal induced abortions, 13.8% in spontaneous abortions, 1.3% in ectopic pregnancies, and 0.5% in fetal deaths. These data can be used to provide denominators for the calculation of a variety of pregnancy outcome-specific rates.