The Meaning of Giving Birth: Voices of Hmong Women Living in Vietnam.

Increasing knowledge about the sociocultural context of birth is essential to promote culturally sensitive nursing care. This qualitative study provides an ethnographic view of the perspectives on birthing of Hmong mothers living in the highlands of Vietnam. Unique cultural beliefs exist in Hmong culture about the spiritual and physical world as well as ritual practices associated with childbearing. This includes variations of ancestor worship, reincarnation, and healing practices by shamans. Traditionally, Hmong families take an active role in childbirth with birth frequently occurring in the home. Situated within a large collaborative anthropology project, a convenience sample of 8 Hmong women, who had recently given birth, were interviewed regarding the perinatal experience. In addition, ethnic traditional birth attendants (midwives) and other village women contributed perspectives providing richly descriptive data. This ethnographic study was conducted during 6 weeks of immersed participant observation with primary data collection carried out through fieldwork. Data were analyzed to derive cultural themes from interviews and observations. Significant themes included (1) valuing motherhood, (2) laboring and giving birth silently, (3) giving birth within the comfort of home and family, (4) feeling capable of birthing well, (5) feeling anxiety to provide for another child, and (6) embracing cultural traditions. Listening to the voices of Hmong women enhances understanding of the meaning of childbirth. Gaining greater understanding of Hmong cultural beliefs and practices can ensure childbearing women receive respectful, safe, and quality care.

Chemical genomic screening reveals synergism between parthenolide and inhibitors of the PI-3 kinase and mTOR pathways.

We have previously shown that the plant-derived compound parthenolide (PTL) can impair the survival and leukemogenic activity of primary human acute myeloid leukemia (AML) stem cells. However, despite the activity of this agent, PTL also induces cellular protective responses that likely function to reduce its overall cytotoxicity. Thus, we sought to identify pharmacologic agents that enhance the antileukemic potential of PTL. Toward this goal, we used the gene expression signature of PTL to identify compounds that inhibit cytoprotective responses by performing chemical genomic screening of the Connectivity Map database. This screen identified compounds acting along the phosphatidylinositol 3-kinase and mammalian target of rapamycin pathways. Compared with single agent treatment, exposure of AML cells to the combination of PTL and phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitors significantly decreased viability of AML cells and reduced tumor burden in vitro and in murine xenotransplantation models. Taken together, our data show that rational drug combinations can be identified using chemical genomic screening strategies and that inhibition of cytoprotective functions can enhance the eradication of primary human AML cells.

Selective activity of the histone deacetylase inhibitor AR-42 against leukemia stem cells: a novel potential strategy in acute myelogenous leukemia.

Most patients with acute myelogenous leukemia (AML) relapse and die of their disease. Increasing evidence indicates that AML relapse is driven by the inability to eradicate leukemia stem cells (LSC). Thus, it is imperative to identify novel therapies that can ablate LSCs. Using an in silico gene expression-based screen for compounds evoking transcriptional effects similar to the previously described anti-LSC agent parthenolide, we identified AR-42 (OSU-HDAC42), a novel histone deacetylase inhibitor that is structurally similar to phenylbutyrate, but with improved activity at submicromolar concentrations. Here, we report that AR-42 induces NF-κB inhibition, disrupts the ability of Hsp90 to stabilize its oncogenic clients, and causes potent and specific cell death of LSCs but not normal hematopoietic stem and progenitor cells. Unlike parthenolide, the caspase-dependent apoptosis caused by AR-42 occurs without activation of Nrf-2-driven cytoprotective pathways. As AR-42 is already being tested in early clinical trials, we expect that our results can be extended to the clinic.

Giving birth: the voices of women in Tamil Nadu, India.

PURPOSE: The purpose of this qualitative descriptive study is to describe the perceptions of childbearing women living in Tamil Nadu, India. This study can increase cultural understanding and foster cultural competence in nurses caring for Indian women. STUDY DESIGN AND METHODS: Women were invited to share their childbearing experiences. Following institutional review board approval, interviews were held with 22 women who had given birth in the previous 18 months to a viable infant. The women were grateful for the opportunity to share their perspectives with an interested nurse investigator. Data collection proceeded concurrently with data analysis. Themes were generated collaboratively by the research team. RESULTS: This research provides insights into the perspectives of mothers living in Tamil Nadu, India. Themes included anticipating becoming a mother, following the advice of mothers-in-law and other "wise" women, fear of childbirth related to lack of knowledge, and valuing support during labor and birth. Others included having the greater blessing of giving birth to a son, making the transition to motherhood, following postpartum rituals/ceremonies, and having a desire to give their child the best that life circumstances allow. CLINICAL IMPLICATIONS: Nurses should be sensitive to the social determinants of health, which frame giving birth. Listening to the voices of women is helpful in guiding clinical practice. Understanding of childbirth practices in culturally diverse women is essential. Potentially harmful practices can be changed through appropriate educational offerings.

Rapid and selective death of leukemia stem and progenitor cells induced by the compound 4-benzyl, 2-methyl, 1,2,4-thiadiazolidine, 3,5 dione (TDZD-8).

Leukemia is thought to arise from malignant stem cells, which have been described for acute and chronic myeloid leukemia (AML and CML) and for acute lymphoblastic leukemia (ALL). Leukemia stem cells (LSCs) are relatively resistant to current chemotherapy and likely contribute to disease relapse and progression. Consequently, the identification of drugs that can efficiently eradicate LSCs is an important priority. In the present study, we investigated the antileukemia activity of the compound TDZD-8. Analysis of primary AML, blast crisis CML (bcCML), ALL, and chronic lymphoblastic leukemia (CLL) specimens showed rapid induction of cell death upon treatment with TDZD-8. In addition, for myeloid leukemias, cytotoxicity was observed for phenotypically primitive cells, in vitro colony-forming progenitors, and LSCs as defined by xenotransplantation assays. In contrast, no significant toxicity was observed for normal hematopoietic stem and progenitor cells. Notably, cell death was frequently evident within 2 hours or less of TDZD-8 exposure. Cellular and molecular studies indicate that the mechanism by which TDZD-8 induces cell death involves rapid loss of membrane integrity, depletion of free thiols, and inhibition of both the PKC and FLT3 signaling pathways. We conclude that TDZD-8 uses a unique and previously unknown mechanism to rapidly target leukemia cells, including malignant stem and progenitor populations.

An orally bioavailable parthenolide analog selectively eradicates acute myelogenous leukemia stem and progenitor cells.

Leukemia stem cells (LSCs) are thought to play a central role in the pathogenesis of acute leukemia and likely contribute to both disease initiation and relapse. Therefore, identification of agents that target LSCs is an important consideration for the development of new therapies. To this end, we have previously demonstrated that the naturally occurring compound parthenolide (PTL) can induce death of human LSCs in vitro while sparing normal hematopoietic cells. However, PTL has relatively poor pharmacologic properties that limit its potential clinical use. Consequently, we generated a family of PTL analogs designed to improve solubility and bioavailability. These studies identified an analog, dimethylamino-parthenolide (DMAPT), which induces rapid death of primary human LSCs from both myeloid and lymphoid leukemias, and is also highly cytotoxic to bulk leukemic cell populations. Molecular studies indicate the prevalent activities of DMAPT include induction of oxidative stress responses, inhibition of NF-kappaB, and activation of p53. The compound has approximately 70% oral bioavailability, and pharmacologic studies using both mouse xenograft models and spontaneous acute canine leukemias demonstrate in vivo bioactivity as determined by functional assays and multiple biomarkers. Therefore, based on the collective preclinical data, we propose that the novel compound DMAPT has the potential to target human LSCs in vivo.