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.     

Histologic changes mimicking biliary disease in liver biopsies with venous outflow impairment.

Impairment of venous outflow from the liver manifests as zone 3 sinusoidal dilatation and congestion (SDC) in liver biopsy. The spectrum of histologic changes in portal tracts has not been described. We studied liver biopsies from 34 patients with a confirmed diagnosis of venous outflow impairment (VOI). Liver transplant recipients and biopsies with cirrhosis and hepatic neoplasms were excluded. Clinical records were reviewed for laboratory tests and radiographic findings. In all, 19 patients had right heart disease, 13 had classic Budd-Chiari syndrome and two had veno-occlusive disease. Liver chemistry tests showed elevated liver transaminases (n=21; 61.8%), elevated alkaline phosphatase (n=31; 91.2%) and GGT (all 13 cases tested). The elevation in ALT and AST was mild (below 200 U/l in all cases), while alkaline phosphatase (ALP) was elevated above 500 U/l in nine (26.5%) patients and above 1000 U/l in three cases. On biopsy, all cases showed SDC. The portal tracts showed (a) portal expansion with bile ductular proliferation (n=16; 47.1%) accompanied by lymphoplasmacytic infiltrate (n=10), lymphocytic cholangitis (n=3) and portal or periportal fibrosis (n=11), (b) Portal and/or periportal fibrosis without ductular proliferation (n=3; 8.8%) or (c) Normal portal tracts (n=15; 44.1%). The combination of elevated ALP and bile ductular changes on biopsy suggested chronic bile duct disease. Ultrasound/CT scan evaluation of bile ducts in 26 patients showed no biliary tree abnormality. Antimitochondrial antibody testing in eight cases also yielded negative results. In conclusion, bile ductular proliferation, portal inflammation and portal-based fibrosis are commonly seen in liver biopsies of patients with VOI even in the absence of bile duct disease. These changes are often accompanied by elevated ALP and GGT and can lead to the suspicion of chronic biliary disease. In the absence of demonstrable abnormalities in the biliary tree, these changes can be attributed to venous outflow impairment.     

Adverse consequences of immediate thrombolysis-related complications: a multi-centre registry-based cohort study of acute stroke

Journal of Thrombosis and Thrombolysis - Complications following thrombolysis for stroke are well documented, and mostly concentrated on haemorrhage. However, the consequences of patients who...     

Correlates of affective empathy,perspective taking,and generativity among a sample of adults

Previous research suggests that empathy can be cultivated by social ideals and relationships with people. The current study examines family importance and religious importance as correlates of affective empathy, perspective taking, and generativity among a sample of adults aged 18 to 35 (N = 722). Given the ethnic and racial diversity represented by Millennials and Generation Z, the moderating role of racial group membership is explored as well. Results indicate that family importance is positively associated with affective empathy, perspective taking, and generativity for the overall sample, though the relationship is particularly strong for non-Hispanic whites. Religious importance is significantly related to affective empathy and generativity (not perspective taking), primarily among Black, Indigenous, and/or People of Color. Due to the increasing visibility of victimization towards socially vulnerable groups, it is important to understand how attitudes oriented towards helping and empathizing with others are fostered. Implications for further research are discussed.     

Thoracic surgery in United Arab Emirates

The United Arab Emirates (UAE) has undergone a significant change in its population and economy in the last decades and in parallel its healthcare system has evolved rapidly to provide advanced, innovative and world-leading care. At the forefront of this revolution in healthcare is the development of a multidisciplinary multimodality thoracic service provision, offered at quaternary referral hospitals amalgamating academics, training, research and innovation. Previously, thoracic service care was limited to single providers at various public and private hospitals, usually performing lower complexity cases. Most complex thoracic cases were repatriated outside the UAE. This practice was replaced with the opening of Cleveland Clinic Abu Dhabi (CCAD), in 2015, which created a multidisciplinary thoracic program. This included the start of a mini-invasive surgical and lung transplantation program. Since that time other public and private hospitals have emerged providing care in a similar model. The impact of these programs has been a decreased transfer of patients abroad for treatment. Under the umbrella of the Emirates Thoracic Society (ETS) a platform for greater collaboration aimed at improving patient care, potential research and physician education has been created. Direct links have been established with world-leading Thoracic surgery and Respiratory Medicine Centers facilitating this development and offering support and guidance. This article charts these changes in thoracic care in the recent past, present, and delineates plans for the future in the UAE.