Search

Research on intimate partner violence shows that individuals who employ abusive behaviors also often have other psychosocial health problems (e.g., substance use) that may limit their ability to engage in treatment for abuse. Limited information exists regarding the psychosocial health needs of individuals who perpetrate abuse and how those needs play a role in their ability to follow through and complete an intervention program. Administrative data from one batterer intervention program (BIP) (N = 330), the local Department of Human Services, and court records were used to explore the relationship of service involvement to post-BIP recidivism. We found that over half the sample had engagement with DHS prior to starting the BIP, and general welfare, health and medical assistance, and behavioral health services were the most accessed programs. Additionally, recidivism for any crime was significantly higher among those with prior DHS involvement. Individuals who perpetrate abuse and who have a history of contact with DHS may represent the most vulnerable population with regards to both risk for attrition from a BIP and future recidivism. Future studies should seek to understand best practices for referrals and coordinated care for individuals who perpetrate abuse and ensure access to a broad range of services to help assist in reducing violent behaviors., Author(s): Penelope K. Morrison [sup.1] , Kelley Jones [sup.2] , Elizabeth Miller [sup.3] , Patricia A. Cluss [sup.4] , Donna George [sup.5] , Rhonda Fleming [sup.6] , Judy C. Chang [...]

Exercise may decrease the incidence of obesity and obesity related complications during pregnancy including gestational diabetes and preeclampsia. African American women are at higher risk for obesity and physical inactivity during pregnancy when compared to other patient groups. The purpose of this qualitative study was to describe in detail the unique beliefs and perspectives regarding exercise during pregnancy of African American women. A series of 6 focus groups discussions with pregnant African American women were audio-recorded and transcribed verbatim. Focus group transcripts were qualitatively analyzed for major themes and independently coded for beliefs regarding exercise during pregnancy. A total of 34 pregnant, African American women participated in 6 focus group discussions. The majority of women were single (94%), had only a high school education (67%), received Medicaid (100%) and had a mean BMI of 33 kg/[m.sup.2]. Three major themes emerged regarding our subjects' beliefs about exercise during pregnancy: (1) women had a broad definition of what types of activities constituted exercise, (2) women believed exercise was generally beneficial during pregnancy and (3) women believed certain types of activities or movements could cause problems with pregnancy. African American women overwhelmingly believe that exercise positively impacts pregnancy. A lack of knowledge concerning the benefits of exercise during pregnancy was not found to be a major contributor to inactivity in African American women. However, health care providers should be aware of cultural myths that prevent many African American women from performing certain activities during pregnancy. Keywords African American * Exercise * Pregnancy, Introduction Maternal obesity is one of the leading causes of maternal and neonatal morbidity during pregnancy. Obese women have greater rates of gestational diabetes, gestational hypertension, preeclampsia, antepartum stillbirth, cesarean [...]

To date, a large number of reports have described reprogramming many somatic cell types into induced pluripotent stem (iPS) cells, using different numbers of transcription factors and devising alternate methods of introducing the transcription factor genes or proteins into the somatic cells. Here, we describe a method using bacteriophage [PHI]C31 integrase to reprogram mouse embryonic fibroblasts and human amniotic fluid cells into iPS cells. These iPS cells showed morphology, surface antigens, gene expression, and epigenetic states similar to ES cells and formed teratomas with three germ layers in nonobese diabetic/severely compromised immunodeficient mice. Importantly, these iPS cells have only a single integration site in each cell line. The locations of integration favor the intergenic regions, and their distances from the adjacent genes extended from several hundred to >1 million bp. The effect of the insertion on the expression of these genes can be studied by RT-PCR. No insertion into microRNA gene loci was detected. Hence, it is possible to select cells in which adjacent gene functions are not affected, or the inserts can be removed if necessary. We conclude that phage integrase-mediated site-specific recombination can produce iPS cells that have undisturbed endogenous gene function and could be safe for future human therapeutic application. amniotic fluid cells | bacterial attachment site | phage attachment site | chromosome localization | [PHI]C31 | plasmid rescue doi/ 10.1073/pnas.1012677107

The innovation of reprogramming somatic cells to induced pluripotent stem cells provides a possible new approach to treat [beta]-thalassemia and other genetic diseases such as sickle cell anemia. Induced pluripotent stem (iPS) cells can be made from these patients' somatic cells and the mutation in the [beta]-globin gene corrected by gene targeting, and the cells differentiated into hematopoietic cells to be returned to the patient. In this study, we reprogrammed the skin fibroblasts of a patient with homozygous [[beta].sup.0] thalassemia into iPS cells, and showed that the iPS cells could be differentiated into hematopoietic cells that synthesized hemoglobin. Prenatal diagnosis and selective abortion have been effective in decreasing the number of [beta]-thalassemia births in some countries that have instituted carrier screening and genetic counseling. To make use of the cells from the amniotic fluid or chorionic villus sampling that are used for prenatal diagnosis, we also showed that these cells could be reprogrammed into iPS cells. This raises the possibility of providing a new option following prenatal diagnosis of a fetus affected by a severe illness. Currently, the parents would choose either to terminate the pregnancy or continue it and take care of the sick child after birth. The cells for prenatal diagnosis can be converted into iPS cells for treatment in the perinatal periods. Early treatment has the advantage of requiring much fewer cells than adult treatment, and can also prevent organ damage in those diseases in which damage can begin in utero or at an early age. amniocentesis | chorionic villus sampling | hematopoietic differentiation | hemoglobin

Health professionals from two different clinical settings were asked about their comfort level in dealing with intimate partner violence (IPV). Focus groups and semistructured interviews were used to gather information. Staff in an obstetrics and gynecology setting relatively rich in IPV resources described feeling capable dealing with IPV. The staff in a general medicine setting dedicated to women's health but without a focus on IPV and with fewer supports described discomfort and difficulty dealing with IPV. Presence of systemic prioritization of and resources for IPV were described as contributing to the confidence in addressing the issue. Other necessary elements identified included (a) on-site resources, (b) adequate time, (c) focused IPV training, and (d) a team or systemic approach. Keywords: intimate partner violence; screening; barriers to care; health care system; coordinated care

Sickle cell anemia is one of the most common genetic diseases worldwide. Patients often suffer from anemia, painful crises, infections, strokes, and cardiopulmonary complications. Although current management has improved the quality of life and survival of patients, cure can be achieved only with bone marrow transplantation when histocompatible donors are available. The ES cell technology suggests that a therapeutic cloning approach may be feasible for treatment of this disease. Using a transgenic/knockout sickle cell anemia mouse model, which harbors 240 kb of human DNA sequences containing the [[beta].sup.S]-globin gene, we prepared ES cells from blastocysts that had the sickle cells anemia genotype and carried out homologous recombination with DNA constructs that contained the [[beta].sup.A]-globin gene. We obtained ES cells in which the/3s was corrected to the [[beta].sup.A] sequence. Hematopoietic cells differentiated from these ES cells produced both hemoglobin A and hemoglobin S. This approach can be applied to human ES cells to correct the sickle mutation as well as [beta]-thalassemia mutations. correction of mutation | homologous recombination | sickle cell anemia | hematopoietic differentiation | [beta]-thalassemia

Sickle cell anemia (SCA) and thalassemia are among the most common genetic diseases worldwide. Current approaches to the development of murine models of SCA involve the elimination of functional murine [Alpha]- and [Beta]-globin genes and substitution with human [Alpha] and [[Beta].sup.s] transgenes. Recently, two groups have produced mice that exclusively express human HbS. The transgenic lines used in these studies were produced by coinjection of human [Alpha]-, [Gamma]-, and [Beta]-globin constructs. Thus, all of the transgenes are integrated at a single chromosomal site. Studies in transgenic mice have demonstrated that the normal gene order and spatial organization of the members of the human [Beta]-globin gene family are required for appropriate developmental and stage-restricted expression of the genes. As the cis-acting sequences that participate in activation and silencing of the [Gamma] and [Beta]-globin genes are not fully defined, murine models that preserve the normal structure of the locus are likely to have significant advantages for validating future therapies for SCA. To produce a model of SCA that recapitulates not only the phenotype, but also the genotype of patients with SCA, we have generated mice that exclusively express HbS after transfer of a 240-kb [[Beta].sup.s] yeast artificial chromosome. These mice have hemolytic anemia, 10% irreversibly sickled cells in their peripheral blood, reticulocytosis, and other phenotypic features of SCA.

About 70% of hepatocellular carcinomas are known to express [Alpha]-fetoprotein, which is normally expressed in fetal but not in adult livers. To induce herpes simplex virus-thymidine kinase expression in these cancer cells, we constructed an adeno-associated viral vector containing the HSV-TK gene under the control of the [Alpha]-fetoprotein enhancer and albumin promoter. We previously demonstrated in vitro that although this vector can transduce a variety of human cells, only transduced AFP and albumin-expressing hepatocellular carcinoma cell lines were sensitive to killing by ganciclovir (GCV). In the present study, we explored the effect of this vector on hepatocellular carcinoma cells in vivo. Subcutaneous tumors generated in nude mice by implanting hepatoceilular carcinoma cells previously transduced with this vector shrank dramatically after treatment with GCV. Bystander effect was also observed on the tumors generated by mixing transduced and untransduced cells. To test whether the tumor cells can be transduced by the virus in vivo, we injected the recombinant adeno-associated virus into tumors generated by untransduced hepatocarcinoma cell line. Tumor growth were retarded after treatment with GCV. These experiments demonstrate the feasibility of in vivo transduction of tumor cell with rAAV.

The locus control region of the [Beta]-globin gene is composed of four erythroid-specific hypersensitive sites. Hypersensitive site 2 has been shown to be a powerful enhancer and contains a tandem repeat sequence for the transcription factors AP1 and NFE2 (activating protein 1 and nuclear factor erythroid 2, respectively). The human NRF2 (NFE2 related factor 2) has been isolated by bacterial expression screening using this core sequence as a probe. p45-NFE2, NRF1, and NRF2 belong to the CNC ('cap 'n' collar') subfamily of the basic region-leucine zipper transcription factors, which exhibits strong homology at specific regions such as the 'CNC' and the DNA binding and leucine zipper domains. Although the erythroid-specific p45-NFE2 has been implicated in globin gene regulation, p45-NFE2 null mice succumb to bleedings due to lack of platelets and those that survive exhibit only a mild anemia. To determine the function of NRF2, which we found to be widely expressed in vivo, we have characterized the genomic structure of the mouse NRF2 gene, disrupted the Nrf2 gene by homologous recombination in mouse embryonic stem cells (ES cells), and generated [NRF2.sup.-/-] mice. Homozygous mutant mice developed normally, were not anemic, reached adulthood, and reproduced. Our studies indicate that NRF2 is dispensable for mouse development.

The occurrence of hematopoietic malignancies intransgenic mice due to the attachment of the locus control region (LCR) to the viral oncogene encoding the simian virus 40 T antigen is discussed. Experimentsinvolve the introduction of an enhancerless Tag gene downstream of a LCR cassette into the germ lines of mice. Tag expression was only detected at high levels in the mouse tumor.

The sequences within the beta-globin 5' DNase I-hypersensitive site 2 (5'HS-2) that are necessary for full enhancer activity in vivo were identified. Several deletion mutants of 5'HS-2 were linked to the human beta-globin gene and their activity was examined in transgenic mice. The results indicate that the nuclear erythroid factor 2/activator protein 1 motif is required for enhancer activity but that other sequences are necessary for full activity.

The effect of HS2 incorporation on gene expression was investigated using murine erythroleukemic cells containing retrovirally transferred human beta-globin genes. HS2 is one of four major DNAse I hypersensitive sites located in the locus control region of the beta-globin cluster. Results show that incorporation into viral constructs of a 36-base pair segment derived from HS2 causes a two-fold increase in beta-globin gene expression. This increase was absent when longer HS2 segments were utilized indicating that the NFE-2/Ap-1 binding sequence contained in the 36-base pair HS2 fragment may be involved in gene expression regulation.

A survey of domestic violence programs across North Carolina in order to examine the extent to which the domestic violence programs served women with particular needs in order to document domestic violence and receive help is discussed. The one tenth of the domestic violence programs were without any staff or volunteers who were trained in dealing with substance abuse is highlighted.