ID4 regulates mammary gland development by suppressing p38MAPK activity.

The ID family of helix-loop-helix proteins regulates cell proliferation and differentiation in many different developmental pathways, but the functions of ID4 in mammary development are unknown. We report that mouse Id4 is expressed in cap cells, basal cells and in a subset of luminal epithelial cells, and that its targeted deletion impairs ductal expansion and branching morphogenesis as well as cell proliferation induced by estrogen and/or progesterone. We discover that p38MAPK is activated in Id4-null mammary cells. p38MAPK is also activated following siRNA-mediated Id4 knockdown in transformed mammary cells. This p38MAPK activation is required for the reduced proliferation and increased apoptosis in Id4-ablated mammary glands. Therefore, ID4 promotes mammary gland development by suppressing p38MAPK activity.

Pregnancy-related knowledge and information needs of women with epilepsy: a systematic review.

For women with epilepsy (WWE), pregnancy is complicated by considerations such as the potential teratogenicity of antiepileptic drugs (AEDs) versus the risks of having seizures during pregnancy. However, qualitative research suggests that many WWE remain uninformed about the risks associated with epilepsy and pregnancy and may, therefore, be making uninformed decisions about their families. The objectives of this review were to determine the level of patient knowledge, their informational needs, and whether these needs concerning pregnancy and childbirth issues are met among WWE. Electronic databases searched were PsycINFO, MEDLINE, Embase, CINAHL, and Web of Science. Studies were included if they used quantitative methods to survey WWE aged 16years or older about their knowledge, access to information, or informational needs specifically regarding epilepsy and pregnancy. Twelve studies were identified and assessed for research standards using the Quality Index. Overall Quality Index score was only 7.1 out of 14, indicating significant design limitations of many included studies, including highly selective sampling methods and the use of unvalidated outcome measures. There was a paucity of studies investigating specific areas of women's knowledge and information needs. Overall, WWE reported adequate awareness, but limited knowledge, of key issues regarding pregnancy and childbirth. Across studies, many women reported not receiving information about these issues. Evidence suggested that many WWE wanted to receive more information - particularly about the risks of AEDs for their offspring - well in advance of choosing an AED or planning pregnancy. Women aged under 35years wanted the most information. Preconception counseling received by many WWE appears insufficient, risking uninformed decision-making about pregnancy. Further research is needed to investigate the barriers that WWE face in accessing, receiving, and retaining appropriate information.

Evaluation of a Decision Aid for Women with Epilepsy Who Are Considering Pregnancy: A Randomized Controlled Trial.

BACKGROUND: For many women with epilepsy (WWE), decision making about pregnancy is complicated by considerations such as the potential teratogenicity of antiepileptic drugs, offspring risk of epilepsy, seizure occurrence during pregnancy, and the challenges of parenting amidst poorly controlled seizures. OBJECTIVE: This proof-of-concept, randomized controlled trial aimed to evaluate a decision aid (DA) developed to help WWE decide if they should start or enlarge their families. METHODS: Seventy-nine WWE of childbearing age were recruited from Epilepsy Action Australia between October and November 2013 and randomized to receive the intervention (the DA) or not, and to complete a set of questionnaires pre- and post- intervention. The DA, delivered as a PDF booklet, provided balanced evidence-based information about options, risks and benefits, including probabilities; as well as steps for clarifying values and considering options within one's personal situation. RESULTS: Compared with the control group, the DA group had statistically significant improvements in knowledge about pregnancy and epilepsy (Cohen's d = 1.24; 95%CI = 0.77 to 1.83) and reduced decisional conflict (Cohen's d = 0.59; 95%CI = 0.21 to 0.99). Changes in decision self-efficacy, certainty of choice, patient-practitioner communication abilities and value congruence with choice were comparable between the DA and control group. Importantly, women's decisions about motherhood were not biased towards either direction, and there were no adverse effects on depression or anxiety. All women who received the DA indicated they would recommend it to other WWE. CONCLUSIONS: The DA has the potential to serve as a useful support tool for WWE who are considering motherhood. Future research is needed to test the DA in clinical settings with guidance from a health professional. The trial was registered with the Australian New Zealand Clinical Trials Registry (ID ACTRN12613001082796).

Cytoglobin is a stress-responsive hemoprotein expressed in the developing and adult brain.

Cytoglobin (Cygb) is a novel tissue hemoprotein relatively similar to myoglobin (Mb). Because Cygb shares several structural features with Mb, we hypothesized that Cygb functions in the modulation of oxygen and nitric oxide metabolism or in scavenging free radicals within a cell. In the present study we examined the spatial and temporal expression pattern of Cygb during murine embryogenesis. Using in situ hybridization, RT-PCR, and Northern blot analyses, limited Cygb expression was observed during embryogenesis compared with Mb expression. Cygb expression was primarily restricted to the central nervous system and neural crest derivatives during the latter stages of development. In the adult mouse, Cygb is expressed in distinct regions of the brain as compared with neuroglobin (Ngb), another globin protein, and these regions are responsive to oxidative stress (i.e., hippocampus, thalamus, and hypothalamus). In contrast to Ngb, Cygb expression in the brain is induced in response to chronic hypoxia (10% oxygen). These results support the hypothesis that Cygb is an oxygen-responsive tissue hemoglobin expressed in distinct regions of thenormoxic and hypoxic brain and may play a key role in the response of the brain to ahypoxic insult.

Alternative therapies for orthotopic heart transplantation.

Heart failure has reached epidemic proportions in the United States. More than 5 million patients are treated for heart failure and approximately a half a million new patients are diagnosed with this disease each year in the United States. Recent pharmacological therapies have been used for the treatment of this patient population, but heart failure remains a major source of morbidity and mortality for patients. Orthotopic heart transplantation is a viable treatment option for heart failure patients; however, cardiac transplantation is limited by the donor availability. Limited donor organ availability has led to the development of alternative therapeutic strategies, including xenotransplantation, mechanical support devices, and cell transfer/tissue engineering protocols. This review highlights the current treatment modalities and emerging strategies for the treatment of advanced heart failure.

Introduction of oncogenes into mammary glands in vivo with an avian retroviral vector initiates and promotes carcinogenesis in mouse models.

We have adapted the avian leukosis virus RCAS (replication-competent avian sarcoma-leukosis virus LTR splice acceptor)-mediated somatic gene transfer technique to introduce oncogenes into mammary cells in mice transgenic for the avian subgroup A receptor gene, tva, under control of the mouse mammary tumor virus (MMTV) promoter. Intraductal instillation of an RCAS vector carrying the polyoma middle T antigen (PyMT) gene (RCAS-PyMT) induced multiple, oligoclonal tumors within 3 weeks in infected mammary glands of MMTV-tva transgenic mice. The rapid appearance of these tumors from a relatively small pool of infected cells (estimated to be approximately 2 x 10(3) cells per gland by infection with RCAS carrying a GFP gene; RCAS-GFP) was accompanied by a high fraction of cells positive for Ki67, Cyclin D1, and c-Myc, implying strong proliferation competence. Furthermore, the tumors displayed greater cellular heterogeneity than did tumors arising in MMTV-PyMT mice, suggesting that RCAS-PyMT transforms a relatively immature cell type. Infection of mice transgenic for both MMTV-Wnt-1 and MMTV-tva with RCAS virus carrying an activated Neu oncogene dramatically enhanced tumor formation over what is observed in uninfected bitransgenic animals. We conclude that infection of mammary glands with retrovirus vectors is an efficient means to screen candidate oncogenes for their capacity to initiate or promote mammary carcinogenesis in the mouse.