The role of aromatase inhibitors in ameliorating deleterious effects of ovarian stimulation on outcome of infertility treatment

Clinical utilization of ovulation stimulation to facilitate the ability of a couple to conceive has not only provided a valuable therapeutic approach, but has also yielded extensive information on the physiology of ovarian follicular recruitment, endometrial receptivity and early embryo competency. One of the consequences of the use of fertility enhancing agents for ovarian stimulation has been the creation of a hyperestrogenic state, which may influence each of these parameters. Use of aromatase inhibitors reduces hyperestrogenism inevitably attained during ovarian stimulation. In addition, the adjunct use of aromatase inhibitors during ovarian stimulation reduces amount of gonadotropins required for optimum stimulation. The unique approach of reducing hyperestrogenism, as well as lowering amount of gonadotropins without affecting the number of mature ovarian follicles is an exciting strategy that could result in improvement in the treatment outcome by ameliorating the deleterious effects of the ovarian stimulation on follicular development, endometrial receptivity, as well as oocyte and embryo quality

Expression pattern and regulation of genes differ between fibroblasts of adhesion and normal human peritoneum

BACKGROUND: Injury to the peritoneum during surgery is followed by a healing process that frequently results in the attachment of adjacent organs by a fibrous mass, referred commonly as adhesions. Because injuries to the peritoneum during surgery are inevitable, it is imperative that we understand the mechanisms of adhesion formation to prevent its occurrence. This requires thorough understanding of the molecular sequence that results in the attachment of injured peritoneum and the development of fibrous tissue. Recent data show that fibroblasts from the injured peritoneum may play a critical role in the formation of adhesion tissues. Therefore, identifying changes in gene expression pattern in the peritoneal fibroblasts during the process may provide clues to the mechanisms by which adhesion develop. METHODS: In this study, we compared expression patterns of larger number of genes in the fibroblasts isolated from adhesion and normal human peritoneum using gene filters. Contributions of TGF-beta1 and hypoxia in the altered expression of specific genes were also examined using a semiquantitative RT-PCR technique. RESULTS: Results show that several genes are differentially expressed between fibroblasts of normal and adhesion peritoneum and that the peritoneal fibroblast may acquire a different phenotype during adhesion formation. Genes that are differentially expressed between normal and adhesion fibroblasts encode molecules involved in cell adhesion, proliferation, differentiation, migration and factors regulating cytokines, transcription, translation and protein/vesicle trafficking. CONCLUSIONS: Our data substantiate that adhesion formation is a multigenic phenomenon and not all changes in gene expression pattern between normal and adhesion fibroblasts are the function of TGF-beta1 and hypoxia that are known to influence adhesion formation. Analysis of the gene expression data in the perspective of known functions of genes connote to additional targets that may be manipulated to inhibit adhesion development

Gestational Sac Aspiration of Heterotopic Ectopic Pregnancy in a Cesarean Section Scar

Background: This article describes a case of heterotopic pregnancy that included a normal twin intrauterine pregnancy and one cesarean section (CS) scar pregnancy diagnosed at 6 weeks of gestation. Ultrasound-guided aspiration of the ectopic gestational sac was performed, and the concurrent twin intrauterine pregnancy (IUP) was preserved successfully. The patient was a 50-year-old woman with secondary infertility. Case: The patient underwent in vitro fertilization and embryo transfer using a donor-egg program to achieve pregnancy with her current partner. At 6-weeks' gestation, she underwent a transvaginal ultrasound scan (US) examination showing a viable twin IUP with a third gestational sac with viable embryo located low within the anterior wall of the uterus. The appearance was consistent with a cesarean scar ectopic pregnancy. This was confirmed on a subsequent US 1 week later. She desired to continue the intrauterine pregnancy. US-guided aspiration of the cesarean scar ectopic pregnancy was attempted. The treatment was successful. Results: The twin pregnancy progressed without further complications. Conclusions: Heterotopic CS ectopic pregnancy can be successfully treated with transvaginal US-guided aspiration. (J GYNECOL SURG 29:317)Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140090/1/gyn.2012.0026.pd

A gorilla adenovirus-based vaccine against Zika virus induces durable immunity and confers protection in pregnancy

The teratogenic potential of Zika virus (ZIKV) has made the development of an effective vaccine a global health priority. Here, we generate two gorilla adenovirus-based ZIKV vaccines that encode for pre-membrane (prM) and envelope (E) proteins (GAd-Zvp) or prM and the ectodomain of E protein (GAd-Eecto). Both vaccines induce humoral and cell-mediated immune responses and prevent lethality after ZIKV challenge in mice. Protection is antibody dependent, CD

A library of infectious hepatitis C viruses with engineered mutations in the E2 gene reveals growth-adaptive mutations that modulate interactions with scavenger receptor class B type I

While natural hepatitis C virus (HCV) infection results in highly diverse quasispecies of related viruses over time, mutations accumulate more slowly in tissue culture, in part because of the inefficiency of replication in cells. To create a highly diverse population of HCV particles in cell culture and identify novel growth-enhancing mutations, we engineered a library of infectious HCV with all codons represented at most positions in the ectodomain of the E2 gene. We identified many putative growth-adaptive mutations and selected nine highly represented E2 mutants for further study: Q412R, T416R, S449P, T563V, A579R, L619T, V626S, K632T, and L644I. We evaluated these mutants for changes in particle-to-infectious-unit ratio, sensitivity to neutralizing antibody or CD81 large extracellular loop (CD81-LEL) inhibition, entry factor usage, and buoyant density profiles. Q412R, T416R, S449P, T563V, and L619T were neutralized more efficiently by anti-E2 antibodies and T416R, T563V, and L619T by CD81-LEL. Remarkably, all nine variants showed reduced dependence on scavenger receptor class B type I (SR-BI) for infection. This shift from SR-BI usage did not correlate with a change in the buoyant density profiles of the variants, suggesting an altered E2-SR-BI interaction rather than changes in the virus-associated lipoprotein-E2 interaction. Our results demonstrate that residues influencing SR-BI usage are distributed across E2 and support the development of large-scale mutagenesis studies to identify viral variants with unique functional properties. IMPORTANCE Characterizing variant viruses can reveal new information about the life cycle of HCV and the roles played by different viral genes. However, it is difficult to recapitulate high levels of diversity in the laboratory because of limitations in the HCV culture system. To overcome this limitation, we engineered a library of mutations into the E2 gene in the context of an infectious clone of the virus. We used this library of viruses to identify nine mutations that enhance the growth rate of HCV. These growth-enhancing mutations reduced the dependence on a key entry receptor, SR-BI. By generating a highly diverse library of infectious HCV, we mapped regions of the E2 protein that influence a key virus-host interaction and provide proof of principle for the generation of large-scale mutant libraries for the study of pathogens with great sequence variability

Seprafilm® adhesion barrier: (1) a review of preclinical, animal, and human investigational studies

The aim of this study was to provide a single site resource for investigators, clinicians, and others seeking preclinical, animal, and human investigational studies concerning the postsurgical, anti-adhesion barrier Seprafilm™ (Genzyme Corporation, Cambridge, MA). All published preclinical, animal, human extra-abdominal research as of July 2011 have been summarized and included in this document. Searches of Medline and EMBASE Drugs and Pharmaceuticals databases were conducted for original preclinical, animal, and human extra-abdominal studies involving Seprafilm. Preclinical, animal, and extra-abdominal human investigational studies are the study selection for this manuscript. Intraabdominal use is discussed in the accompanying manuscript. Data extraction includes systematic manuscript review. Summary of preclinical, animal, and extra-abdominal human investigational use of Seprafilm by surgical discipline were gathered for data synthesis. The clinical use of Seprafilm, which was approved by the FDA for intra-abdominal procedures, is supported by preclinical and animal studies relating to general surgical and obstetrical/gynecological applications. Findings from preclinical, animal, and human investigational studies at other sites throughout the body raises the potential for additional human clinical trials to assess efficacy and safety following surgical procedures at non-abdominal locations

Post-Ablation Cavity Evaluation: A Prospective Multicenter Observational Clinical Study to Evaluate Hysteroscopic Access to the Uterine Cavity 4 Years after Water Vapor Endometrial Ablation for the Treatment of Heavy Menstrual Bleeding

Study Objective: Patients who have undergone endometrial ablation may present a diagnostic challenge when they subsequently develop vaginal bleeding, pelvic pain, or postmenopausal bleeding. Extensive scarring of the uterine cavity often precludes evaluation and/or conservative treatment. For further research on this topic, we performed hysteroscopic examination in study subjects a mean duration of 4 years after they had undergone water vapor endometrial ablation. Design: Prospective, multicenter, observational clinical study. Setting: Eight private practice or outpatient sites in the United States and Mexico. Patients: Seventy subjects who had completed their 36-month follow-up in the AEGEA Pivotal Trial. Interventions: Diagnostic hysteroscopy. Measurements and Main Results: The subjects were screened for general health and infection and underwent diagnostic hysteroscopy. Menstrual bleeding status was recorded. The video of the hysteroscopic examination was analyzed by an independent reviewer, who assessed uterine cavity access and visualization of the cornua and tubal ostia as well as characterized adhesions on the basis of the criteria by March et al. An independent reviewer also subjectively assessed whether Pipelle endometrial biopsy or intrauterine device placement would be feasible. Uterine cavity access was achieved in 90% (63/70) of subjects. Among subjects with cavity access, the cornua and ostia were visualized in 79% (50/63) and adhesions were absent in 75% (47/63), with only 2 women having severe adhesions (3%, 2/63). Biopsy was projected to be feasible in 86% (62/70) and intrauterine device placement in 60% (42/70) of all subjects. The subjects’ bleeding statuses were not correlated with uterine cavity access. The results were consistent for subjects with large uterine cavities and International Federation of Gynecologic and Obstetrics type II to VI myomas ≤4 cm. Conclusion: Water vapor endometrial ablation preserved an accessible uterine cavity and visualization of the ostia in most subjects, with minimal incidence of severe adhesions, a mean of 4 years after the ablation procedure

Cigarette sources for teens by grade: Implications for prevention and intervention

Objective: To identify at-risk teen populations and their sources of cigarettes, in order to help target future efforts in prevention of teen smoking. Methods: Analysis of smoking behavior questions for students in grades 6, 7, 9 and 12 from the 1997 Pennsylvania Biennial Youth Risk Survey. Results: Current smoking prevalence was 20.9% overall. The number of ninth grade smokers was almost five times higher than the number of sixth grade smokers (30.6% vs. 6.6%). Seventy-three percent of the teens identified friends as a source of tobacco. Stores became the most common source for twelfth graders only. Conclusion: Teenage smoking remains a serious public health concern and easy access to tobacco persists, despite recent legislation. The significant increase in smoking between 6th and 9th graders and the high social availability of cigarettes demonstrate the need for continued attempts to limit teen\u27s access to tobacco and emphasis on prevention efforts in younger adolescents

Human monoclonal antibodies against NS1 protein protect against lethal West Nile virus infection

Envelope protein-targeted vaccines for flaviviruses are limited by concerns of antibody-dependent enhancement (ADE) of infections. Nonstructural protein 1 (NS1) provides an alternative vaccine target that avoids this risk since this protein is absent from the virion. Beyond its intracellular role in virus replication, extracellular forms of NS1 function in immune modulation and are recognized by host-derived antibodies. The rational design of NS1-based vaccines requires an extensive understanding of the antigenic sites on NS1, especially those targeted by protective antibodies. Here, we isolated human monoclonal antibodies (MAbs) from individuals previously naturally infected with WNV, mapped their epitopes using structure-guided mutagenesis, and evaluated their efficac