Long-term effects on nursing alumni: Assessing a course in public and global health.

The impact of a cultural awareness course among nursing students may affect the particular person for years to come. Cultural awareness can be taught via many methods, often requiring study abroad and/or extreme investment of time, money and effort. There is little research on sustained effects on nursing alumni from such a course. The purpose of this descriptive survey study was to determine the long term outcomes of a cultural awareness course and 2) compare the long term effects between alumni who went abroad and those who chose to complete the course locally. One hundred and twenty-one nursing alumni completed the International Education Survey (IES) (Zorn, 1996) with additional open-ended questions. Quantitative and qualitative results concluded: 1) nursing alumni were influenced long term by a course dedicated to public and global health and 2) all alumni had statistically significant IES scores but alumni who studied abroad had the greatest increase.

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.

Honoring Motherhood: The Meaning of Childbirth for Tongan Women.

PURPOSE: The purpose of this ethnographic study was to describe the meaning of childbirth for Tongan women. STUDY DESIGN AND METHODS: In this qualitative descriptive study, 38 Tongan women, 18 from Tonga and 20 from the United States, who had given birth in the past year were invited to share their perceptions of childbirth. Themes were generated collaboratively by the research team. FINDINGS: The overarching theme was honoring motherhood; other themes include using strength to facilitate an unmedicated vaginal birth, describing the spiritual dimensions of birth, adhering to cultural practices associated with childbearing, and the influence of the concept of respect on childbearing. IMPLICATIONS FOR CLINICAL PRACTICE: Understanding the value Tongan women and their families place on motherhood can help nurses to give culturally sensitive nursing care. Tongan beliefs and cultural practices should be respected. Nurses should assess women's personal preferences for their care and advocate for them as needed. Sensitivity to stoicism is important, especially on pain control and patient education. Nurses should be aware of Tongan values regarding modesty and respect, and provide an appropriate care environment. A culturally competent nurse understands the importance of sociocultural influences on women's health beliefs and behaviors and generates appropriate interventions.

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.

Targeting aberrant glutathione metabolism to eradicate human acute myelogenous leukemia cells.

The development of strategies to eradicate primary human acute myelogenous leukemia (AML) cells is a major challenge to the leukemia research field. In particular, primitive leukemia cells, often termed leukemia stem cells, are typically refractory to many forms of therapy. To investigate improved strategies for targeting of human AML cells we compared the molecular mechanisms regulating oxidative state in primitive (CD34(+)) leukemic versus normal specimens. Our data indicate that CD34(+) AML cells have elevated expression of multiple glutathione pathway regulatory proteins, presumably as a mechanism to compensate for increased oxidative stress in leukemic cells. Consistent with this observation, CD34(+) AML cells have lower levels of reduced glutathione and increased levels of oxidized glutathione compared with normal CD34(+) cells. These findings led us to hypothesize that AML cells will be hypersensitive to inhibition of glutathione metabolism. To test this premise, we identified compounds such as parthenolide (PTL) or piperlongumine that induce almost complete glutathione depletion and severe cell death in CD34(+) AML cells. Importantly, these compounds only induce limited and transient glutathione depletion as well as significantly less toxicity in normal CD34(+) cells. We further determined that PTL perturbs glutathione homeostasis by a multifactorial mechanism, which includes inhibiting key glutathione metabolic enzymes (GCLC and GPX1), as well as direct depletion of glutathione. These findings demonstrate that primitive leukemia cells are uniquely sensitive to agents that target aberrant glutathione metabolism, an intrinsic property of primary human AML cells.

Novel mTOR inhibitory activity of ciclopirox enhances parthenolide antileukemia activity.

Ciclopirox, an antifungal agent commonly used for the dermatologic treatment of mycoses, has been shown recently to have antitumor properties. Although the exact mechanism of ciclopirox is unclear, its antitumor activity has been attributed to iron chelation and inhibition of the translation initiation factor eIF5A. In this study, we identify a novel function of ciclopirox in the inhibition of mTOR. As with other mTOR inhibitors, we show that ciclopirox significantly enhances the ability of the established preclinical antileukemia compound, parthenolide, to target acute myeloid leukemia. The combination of parthenolide and ciclopirox demonstrates greater toxicity against acute myeloid leukemia than treatment with either compound alone. We also demonstrate that the ability of ciclopirox to inhibit mTOR is specific to ciclopirox because neither iron chelators nor other eIF5A inhibitors affect mTOR activity, even at high doses. We have thus identified a novel function of ciclopirox that might be important for its antileukemic activity.

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.

Postpartum depression and help-seeking behaviors in immigrant Hispanic women.

OBJECTIVES: To describe perceptions of immigrant Hispanic women experiencing symptoms of postpartum depression (PPD) and to identify barriers to seeking mental health services. DESIGN: Qualitative descriptive. SETTING: Community health clinic. PARTICIPANTS: Twenty immigrant Hispanic women scoring positive for symptoms of PPD receiving health care at a community health clinic who declined mental health services participated in audiotaped interviews held in their homes. METHODS: Following Institutional Review Board approval and informed consent, interviews were conducted with study participants. Transcribed data were analyzed as appropriate for qualitative inquiry. RESULTS: Some of the women did not recognize and/or denied their symptoms attributing their sadness to financial concerns, family relationships, and/or work stressors. Study participants articulately described their symptoms and identified personal barriers including beliefs about emotional health, the perceived stigma of mental illness, hesitancy to seek treatment for symptoms of PPD, and cultural beliefs about motherhood and the role of women. Social barriers included inadequate social support, immigration status, and limited English proficiency. Health care delivery barriers included financial and time constraints and lack of child care and transportation. CONCLUSION: Limited social networks and barriers to health care should be addressed to foster positive outcomes. Mental health services should be embedded with primary health care or obstetric care clinics to facilitate access. Personal and professional support can make a significant contribution to the reduction of symptoms of PPD.

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.

Postpartum depression and culture: Pesado Corazon.

The purpose of this article is to describe what the literature has shown about postpartum depression (PPD) in culturally diverse women. The majority of qualitative studies done with women identified as having PPD have been conducted with Western women, with the second largest group focusing on Chinese women. This article reviews the qualitative studies in the literature and discusses how the management of PPD in technocentric and ethnokinship cultures differs. Social support has been shown to be significantly related to fewer symptoms of PPD, and culturally prescribed practices may or may not be cultural mediators in decreasing the incidence of PPD. Nurses should be sensitive to the varied ways in which culturally diverse women perceive, explain, and report symptoms of PPD. Exemplary interventions for culturally diverse women suffering from PPD are examined in this article as well, although it is clear that additional research is needed to develop models for culturally competent interventions for PPD in culturally diverse women and to document the outcomes of such interventions.

Giving birth: the voices of Ecuadorian women.

PURPOSE: The purpose of this ethnographic study was to describe the perceptions of Ecuadorian childbearing women BACKGROUND: No studies published in English could be found documenting the perspectives of Ecuadorian childbearing women about their birth experiences. METHOD: Thirty-two women who had recently given birth in Guayaquil, Ecuador participated in audiotaped interviews, which were analyzed as appropriate for ethnographic inquiry. RESULTS: "Enduring birth to obtain the gift" was the overarching theme. Supporting themes included caring for self and accessing prenatal care to have a healthy newborn; relying on God to ensure positive maternal/newborn outcomes; submission of self to healthcare providers because of fear, pain, and lack of education; and valuing motherhood. The focus was on the well-being of the child rather than the quality of the birth experience. IMPLICATIONS FOR CLINICAL PRACTICE: With a growing population of women of childbearing age immigrating into the United States from Central and South America, the need for culturally competent care is increasing. Sensitivity to the cultural beliefs and practices of Hispanic and other culturally diverse childbearing women is critical. Women's reliance on God to ensure positive outcomes should be respected. The provision of education and supportive care will help ensure positive outcomes in culturally diverse women.

Discovery of agents that eradicate leukemia stem cells using an in silico screen of public gene expression data.

Increasing evidence indicates that malignant stem cells are important for the pathogenesis of acute myelogenous leukemia (AML) and represent a reservoir of cells that drive the development of AML and relapse. Therefore, new treatment regimens are necessary to prevent relapse and improve therapeutic outcomes. Previous studies have shown that the sesquiterpene lactone, parthenolide (PTL), ablates bulk, progenitor, and stem AML cells while causing no appreciable toxicity to normal hematopoietic cells. Thus, PTL must evoke cellular responses capable of mediating AML selective cell death. Given recent advances in chemical genomics such as gene expression-based high-throughput screening (GE-HTS) and the Connectivity Map, we hypothesized that the gene expression signature resulting from treatment of primary AML with PTL could be used to search for similar signatures in publicly available gene expression profiles deposited into the Gene Expression Omnibus (GEO). We therefore devised a broad in silico screen of the GEO database using the PTL gene expression signature as a template and discovered 2 new agents, celastrol and 4-hydroxy-2-nonenal, that effectively eradicate AML at the bulk, progenitor, and stem cell level. These findings suggest the use of multicenter collections of high-throughput data to facilitate discovery of leukemia drugs and drug targets.

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.

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.

Detection of resistance to acetolactate synthase inhibitors in weeds with emphasis on DNA-based techniques: a review.

Resistance to herbicides inhibiting acetolactate synthase (ALS) has been increasing at a faster rate than in any other herbicide group. The great majority of these cases are due to various single-nucleotide polymorphisms in the ALS gene endowing target site resistance. Many diagnostic techniques have been devised in order to confirm resistance and help producers to adopt the best management strategies. Recent advances in DNA technologies coupled with the knowledge of sequence information have allowed the development of accurate and rapid diagnostic tests. While whole plant-based diagnostic techniques such as seedling bioassays or enzyme-based in vitro bioassays provide accurate results, they tend to be labour- and/or space-intensive and will only respond to the particular herbicides tested, making resolution of cross-resistance patterns more difficult. Successful DNA-based diagnosis of ALS inhibitor resistance has been achieved with three main techniques, (1) restriction fragment length polymorphism, (2) polymerase chain reaction amplification of specific alleles and (3) denaturing high-performance liquid chromatography. All DNA-based techniques are relatively rapid and provide clear identification of the mutations causing resistance. Resistance based on non-target mechanisms is not identified by these DNA-based methods; however, given the prevalence of target site-based ALS inhibitor resistance, this is a minor inconvenience.