ABSTRACT
Chronic hepatitis B is globally prevalent and is a major cause of cirrhosis and hepatocellular carcinoma. Despite immunoprophylaxis against hepatitis B in pregnancy, perinatal transmission still occurs in at least 10% of the children born to a mother with high level of viremia. Decisions regarding hepatitis B therapy during pregnancy must take into account the benefits and safety for both the mother and the unborn baby. In this review, we summarize the current treatment options for chronic hepatitis B with a focus on management during pregnancy and the evidence-based strategies to prevent vertical transmission of hepatitis B virus (HBV).
ABSTRACT
GNAS mutations leading to constitutively active stimulatory G protein alpha-subunit (Gsα) cause different tumors, fibrous dysplasia of bone, and McCune-Albright syndrome, which are typically not associated with short stature. Enhanced signaling of the parathyroid hormone/parathyroid hormone-related peptide receptor, which couples to multiple G proteins including Gsα, leads to short bones with delayed endochondral ossification. It has remained unknown whether constitutive Gsα activity also impairs bone growth. Here we generated mice expressing a constitutively active Gsα mutant (Gsα-R201H) conditionally upon Cre recombinase (cGsαR201H mice). Gsα-R201H was expressed in cultured bone marrow stromal cells from cGsαR201H mice upon adenoviral-Cre transduction. When crossed with mice in which Cre is expressed in a tamoxifen-regulatable fashion (CAGGCre-ER™), tamoxifen injection resulted in mosaic expression of the transgene in double mutant offspring. We then crossed the cGsαR201H mice with Prx1-Cre mice, in which Cre is expressed in early limb-bud mesenchyme. The double mutant offspring displayed short limbs at birth, with narrow hypertrophic chondrocyte zones in growth plates and delayed formation of secondary ossification center. Consistent with enhanced Gsα signaling, bone marrow stromal cells from these mice demonstrated increased levels of c-fos mRNA. Our findings indicate that constitutive Gsα activity during limb development disrupts endochondral ossification and bone growth. Given that Gsα haploinsufficiency also leads to short bones, as in patients with Albright's hereditary osteodystrophy, these results suggest that a tight control of Gsα activity is essential for normal growth plate physiology.
Subject(s)
GTP-Binding Protein alpha Subunits, Gs/metabolism , Animals , Bone Development/genetics , Bone Development/physiology , Cells, Cultured , Chromogranins/genetics , Chromogranins/metabolism , Cyclic AMP/metabolism , Female , GTP-Binding Protein alpha Subunits, Gs/genetics , Integrases/genetics , Integrases/metabolism , Male , Mesenchymal Stem Cells/metabolism , Mesoderm/metabolism , Mice , Mice, Transgenic , Osteogenesis/genetics , Osteogenesis/physiology , Pseudohypoparathyroidism/genetics , Pseudohypoparathyroidism/metabolism , Tamoxifen/pharmacologyABSTRACT
BACKGROUND: Numerous abstracts related to inflammatory bowel disease (IBD) are presented at national conferences in the USA. The overall rate of publication of these abstracts as complete manuscripts is unknown . METHODS: Abstracts submitted to the 2010 American College of Gastroenterology (ACG), Advances in Inflammatory Bowel Diseases (AIBD), and the American Gastroenterological Association abstracts at Digestive Disease Week (DDW) were reviewed. Each abstract was reviewed manually by two authors for type of research, study design, patient population, and outcome. Both PubMed and Google were then searched to determine whether the abstract was published as a full manuscript within five years of the conference. Univariate and multivariate logistic regression analysis was carried out using Stata 14.1. RESULTS: In total, 872 abstracts were reviewed. 49% (426/872) were published as complete manuscripts within five years of the conference. The average length of time to publication was 1.87 years (range 0-5). 42% of abstracts from ACG, 58% from AIBD, and 23% from DDW were eventually published (p < 0.0001). However, abstracts presented at DDW had the shortest time to publication compared to the other conferences (p = 0.002). Factors predictive of eventual publication include: number of authors (mean 7.5 for published vs 6.4 for unpublished p = 0.0001), clinical research compared to basic and translational (p = 0.026), and studies assessing drug safety with no adverse effects reported (p = 0.006). CONCLUSION: Nearly 50% of the abstracts presented at major gastroenterology conferences in the USA are published as full manuscripts 5 years after the conference. Further studies are needed to assess why so many abstracts are not published.
