Applying Anti Oppressive, Empowerment, and Strengths Based Approaches to Social Work Practice with Hmong Clients

This conceptual article discusses social work practice with Hmong Americans using a framework that embraces anti-oppressive practice, empowerment and strengths-based approaches. Specifically, the Hmong kinship social construct of kwv tij neej tsa (pronounced: ku tee ning ja) is used to elaborate on the importance of upholding family relationships that transcends the worker-client relationship. Social workers are encouraged to empower Hmong to seek and ask for resources that support their collective value of connection to family and group identity, which is a strength that contributes to resilience and buffers against historically oppressive practices and systems

Analysis of phosphatases in ER-negative breast cancers identifies DUSP4 as a critical regulator of growth and invasion.

Estrogen receptor (ER)-negative cancers have a poor prognosis, and few targeted therapies are available for their treatment. Our previous analyses have identified potential kinase targets critical for the growth of ER-negative, progesterone receptor (PR)-negative and HER2-negative, or "triple-negative" breast cancer (TNBC). Because phosphatases regulate the function of kinase signaling pathways, in this study, we investigated whether phosphatases are also differentially expressed in ER-negative compared to those in ER-positive breast cancers. We compared RNA expression in 98 human breast cancers (56 ER-positive and 42 ER-negative) to identify phosphatases differentially expressed in ER-negative compared to those in ER-positive breast cancers. We then examined the effects of one selected phosphatase, dual specificity phosphatase 4 (DUSP4), on proliferation, cell growth, migration and invasion, and on signaling pathways using protein microarray analyses of 172 proteins, including phosphoproteins. We identified 48 phosphatase genes are significantly differentially expressed in ER-negative compared to those in ER-positive breast tumors. We discovered that 31 phosphatases were more highly expressed, while 11 were underexpressed specifically in ER-negative breast cancers. The DUSP4 gene is underexpressed in ER-negative breast cancer and is deleted in approximately 50 % of breast cancers. Induced DUSP4 expression suppresses both in vitro and in vivo growths of breast cancer cells. Our studies show that induced DUSP4 expression blocks the cell cycle at the G1/S checkpoint; inhibits ERK1/2, p38, JNK1, RB, and NFkB p65 phosphorylation; and inhibits invasiveness of TNBC cells. These results suggest that that DUSP4 is a critical regulator of the growth and invasion of triple-negative breast cancer cells

Determining exciton bandwidth and film microstructure in polythiophene films using linear absorption spectroscopy

We analyze the linear absorption spectrum of regioregular poly(3-hexylthiophene) films spun from a variety of solvents to probe directly the film microstructure and how it depends on processing conditions. We estimate the exciton bandwidth and the percentage of the film composed of aggregates quantitatively using a weakly interacting H-aggregate model. This provides a description of the degree and quality of crystallites within the film and is in turn correlated with thin-film field-effect transistor characteristics.Comment: Applied Physics Letters (in press); 9 pages, three figure

The promise of microarrays in the management and treatment of breast cancer

Breast cancer is the most common malignancy afflicting women from Western cultures. Developments in breast cancer molecular and cellular biology research have brought us closer to understanding the genetic basis of this disease. Recent advances in microarray technology hold the promise of further increasing our understanding of the complexity and heterogeneity of this disease, and providing new avenues for the prognostication and prediction of breast cancer outcomes. These new technologies have some limitations and have yet to be incorporated into clinical use, for both the diagnosis and treatment of women with breast cancer. The most recent application of microarray genomic technologies to studying breast cancer is the focus of this review

Client satisfaction and experience of telemedicine and home use of mifepristone and misoprostol for abortion up to 10 weeks' gestation at British Pregnancy Advisory Service: A cross-sectional evaluation.

OBJECTIVE: Evaluate satisfaction and experience with telemedicine consultation and home use of mifepristone and misoprostol for abortion to 10 weeks' gestation. STUDY DESIGN: Cross-sectional evaluation of British Pregnancy Advisory Service (BPAS) clients who used mifepristone and misoprostol at home from 11 May to 10 July 2020. We sent a text message with a link to a web-survey 2 to 3 weeks postabortion. Questions assessed satisfaction and experiences with a service model including telephone consultation and provision of medicines by mail or collection from the clinic. We used bivariate and multivariate regression to explore associations between client characteristics and outcomes. Our primary outcomes were overall satisfaction (5-point Likert scale) and reported contact with a health care provider. RESULTS: A total of 1,333 clients participated. Respondents described home use of medications as "straightforward" (75.8%) and most were "very satisfied" (78.3%) or "satisfied" (18.6%) overall. Being "very satisfied" was associated with parity (aOR 1.53, 95% CI 1.09-2.14) and pain control satisfaction (aOR 2.22, 95% CI 1.44-3.44). Health care provider contact was reported by 14.7%; mainly to BPAS' telephone aftercare service (76.8%). Dissatisfaction with pain control (aOR 3.62, 95% CI 1.79-7.29) and waiting >1 week to use mifepristone (aOR3.71, 95% CI 1.48-9.28) were associated with health care provider contact. If needed in the future, most would prefer consultation by phone (74.3%) and home use of mifepristone and misoprostol (77.8%). CONCLUSIONS: Satisfaction with telemedicine and home use of mifepristone and misoprostol is high. Most clients do not need health care provider support when administering medicines at home or post abortion

Using the posterior distribution of deviance to measure evidence of association for rare susceptibility variants

Aitkin recently proposed an integrated Bayesian/likelihood approach that he claims is general and simple. We have applied this method, which does not rely on informative prior probabilities or large-sample results, to investigate the evidence of association between disease and the 16 variants in the KDR gene provided by Genetic Analysis Workshop 17. Based on the likelihood of logistic regression models and considering noninformative uniform prior probabilities on the coefficients of the explanatory variables, we used a random walk Metropolis algorithm to simulate the distributions of deviance and deviance difference. The distribution of probability values and the distribution of the proportions of positive deviance differences showed different locations, but the direction of the shift depended on the genetic factor. For the variant with the highest minor allele frequency and for any rare variant, standard logistic regression showed a higher power than the novel approach. For the two variants with the strongest effects on Q1 under a type I error rate of 1%, the integrated approach showed a higher power than standard logistic regression. The advantages and limitations of the integrated Bayesian/likelihood approach should be investigated using additional regions and considering alternative regression models and collapsing methods

CREB is a critical regulator of normal hematopoiesis and leukemogenesis

The cAMP-responsive element binding protein (CREB) is a 43-kDa nuclear transcription factor that regulates cell growth, memory, and glucose homeostasis. We showed previously that CREB is amplified in myeloid leukemia blasts and expressed at higher levels in leukemia stem cells from patients with myeloid leukemia. CREB transgenic mice develop myeloproliferative disease after 1 year, but not leukemia, suggesting that CREB contributes to but is not sufficient for leukemogenesis. Here, we show that CREB is most highly expressed in lineage negative hematopoietic stem cells (HSCs). To understand the role of CREB in hematopoietic progenitors and leukemia cells, we examined the effects of RNA interference (RNAi) to knock down CREB expression in vitro and in vivo. Transduction of primary HSCs or myeloid leukemia cells with lentiviral CREB shRNAs resulted in decreased proliferation of stem cells, cell- cycle abnormalities, and inhibition of CREB transcription. Mice that received transplants of bone marrow transduced with CREB shRNA had decreased committed progenitors compared with control mice. Mice injected with Ba/F3 cells expressing either Bcr-Abl wild-type or T315I mutation with CREB shRNA had delayed leukemic infiltration by bioluminescence imaging and prolonged median survival. Our results suggest that CREB is critical for normal myelopoiesis and leukemia cell proliferation

STROGAR – STrengthening the Reporting Of Genetic Association studies in Radiogenomics

AbstractDespite publication of numerous radiogenomics studies to date, positive single nucleotide polymorphism (SNP) associations have rarely been reproduced in independent validation studies. A major reason for these inconsistencies is a high number of false positive findings because no adjustments were made for multiple comparisons. It is also possible that some validation studies were false negatives due to methodological shortcomings or a failure to reproduce relevant details of the original study. Transparent reporting is needed to ensure these flaws do not hamper progress in radiogenomics. In response to the need for improving the quality of research in the area, the Radiogenomics Consortium produced an 18-item checklist for reporting radiogenomics studies. It is recognised that not all studies will have recorded all of the information included in the checklist. However, authors should report on all checklist items and acknowledge any missing information. Use of STROGAR guidelines will advance the field of radiogenomics by increasing the transparency and completeness of reporting

Vascular histone deacetylation by pharmacological HDAC inhibition

HDAC inhibitors can regulate gene expression by post-translational modification of histone as well as nonhistone proteins. Often studied at single loci, increased histone acetylation is the paradigmatic mechanism of action. However, little is known of the extent of genome-wide changes in cells stimulated by the hydroxamic acids, TSA and SAHA. In this article, we map vascular chromatin modifications including histone H3 acetylation of lysine 9 and 14 (H3K9/14ac) using chromatin immunoprecipitation (ChIP) coupled with massive parallel sequencing (ChIP-seq). Since acetylation-mediated gene expression is often associated with modification of other lysine residues, we also examined H3K4me3 and H3K9me3 as well as changes in CpG methylation (CpG-seq). RNA sequencing indicates the differential expression of ∼30% of genes, with almost equal numbers being up- and down-regulated. We observed broad deacetylation and gene expression changes conferred by TSA and SAHA mediated by the loss of EP300/CREBBP binding at multiple gene promoters. This study provides an important framework for HDAC inhibitor function in vascular biology and a comprehensive description of genome-wide deacetylation by pharmacological HDAC inhibition

Inhibition of iNOS as a Novel Effective Targeted Therapy Against Triple-Negative Breast Cancer

INTRODUCTION: Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer with no effective targeted therapy. Inducible nitric oxide synthase (iNOS) is associated with poor survival in patients with breast cancer by increasing tumor aggressiveness. This work aimed to investigate the potential of iNOS inhibitors as a targeted therapy for TNBC. We hypothesized that inhibition of endogenous iNOS would decrease TNBC aggressiveness by reducing tumor initiation and metastasis through modulation of epithelial-mesenchymal transition (EMT)-inducing factors. METHODS: iNOS protein levels were determined in 83 human TNBC tissues and correlated with clinical outcome. Proliferation, mammosphere-forming efficiency, migration, and EMT transcription factors were assessed in vitro after iNOS inhibition. Endogenous iNOS targeting was evaluated as a potential therapy in TNBC mouse models. RESULTS: High endogenous iNOS expression was associated with worse prognosis in patients with TNBC by gene expression as well as immunohistochemical analysis. Selective iNOS (1400 W) and pan-NOS (L-NMMA and L-NAME) inhibitors diminished cell proliferation, cancer stem cell self-renewal, and cell migration in vitro, together with inhibition of EMT transcription factors (Snail, Slug, Twist1, and Zeb1). Impairment of hypoxia-inducible factor 1α, endoplasmic reticulum stress (IRE1α/XBP1), and the crosstalk between activating transcription factor 3/activating transcription factor 4 and transforming growth factor β was observed. iNOS inhibition significantly reduced tumor growth, the number of lung metastases, tumor initiation, and self-renewal. CONCLUSIONS: Considering the effectiveness of L-NMMA in decreasing tumor growth and enhancing survival rate in TNBC, we propose a targeted therapeutic clinical trial by re-purposing the pan-NOS inhibitor L-NMMA, which has been extensively investigated for cardiogenic shock as an anti-cancer therapeutic