[Show abstract][Hide abstract] ABSTRACT: β-thalassemia, one of the most common genetic diseases worldwide, is caused by mutations in the human hemoglobin beta (HBB) gene. Creation of human induced pluripotent stem cells (iPSCs) from β-thalassemia patients could offer an approach to cure this disease. Correction of the disease-causing mutations in iPSCs could restore normal function and provide a rich source of cells for transplantation. In this study, we used the latest gene-editing tool, CRISPR/Cas9 technology, combined with the piggyBac transposon to efficiently correct the HBB mutations in patient-derived iPSCs without leaving any residual footprint. No off-target effects were detected in the corrected iPSCs, and the cells retain full pluripotency and exhibit normal karyotypes. When differentiated into erythroblasts using a monolayer culture, gene-corrected iPSCs restored expression of HBB compared to the parental iPSCs line. Our study provides an effective approach to correct HBB mutations without leaving any genetic footprint in patient-derived iPSCs, thereby demonstrating a critical step toward the future application of stem cell-based gene therapy to monogenic diseases.
Genome Research 08/2014; 24:1526-1533. · 13.85 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Intimate partner violence (IPV) is a prevalent, complex, and challenging women's health problem associated with a number of negative medical, reproductive, and mental health conditions. When clinicians bring up the topic with their patients, patients are more likely to disclose. Supportive counseling and referrals are associated with improved safety and health.
Cleveland Clinic Journal of Medicine 07/2014; 81(7):439-446. · 3.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Children whose mothers are victims of intimate partner violence (IPV) are at increased risk of adverse health and psychosocial consequences, including becoming victims or perpetrators of violence in their own relationships. This study aimed to understand the role mothers may play in preventing the perpetuation of violence in their children's lives. We performed semistructured interviews with 18 IPV victims who are mothers and were living at the Women's Center & Shelter of Greater Pittsburgh from July through November 2011. We sought to understand how they communicate with their children about IPV and relationships. These mothers described a desire to explain their IPV experience and offer advice about avoiding violence in relationships. As foundations for these discussions, they emphasized the importance of close relationships and open communication with their children. Although mothers are interested in talking about IPV and relationships and identify communication strategies for doing so, many have never discussed these topics with their children. These mothers need and want an intervention to help them learn how to communicate with their children to promote healthy relationships. Development of a program to facilitate communication between IPV victims and their children could create an important tool to empower mothers to break the cross-generational cycle of domestic violence.
Journal of Interpersonal Violence 06/2014; · 1.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Individuals homozygous for the C-C chemokine receptor type 5 gene with 32-bp deletions (CCR5Δ32) are resistant to HIV-1 infec-tion. In this study, we generated induced pluripotent stem cells (iPSCs) homozygous for the naturally occurring CCR5Δ32 mutation through genome editing of wild-type iPSCs using a combination of transcription activator-like effector nucleases (TALENs) or RNA-guided clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 together with the piggyBac technology. Remark-ably, TALENs or CRISPR-Cas9–mediated double-strand DNA breaks resulted in up to 100% targeting of the colonies on one allele of which biallelic targeting occurred at an average of 14% with TALENs and 33% with CRISPR. Excision of the piggyBac using transposase seamlessly reproduced exactly the naturally occurring CCR5Δ32 mutation without detectable exogenous sequences. We differentiated these modified iPSCs into monocytes/macrophages and demonstrated their resistance to HIV-1 challenge. We propose that this strategy may provide an approach toward a functional cure of HIV-1 infection. homologous recombination | TTAA site | off-site target | cellular therapy T he C-C chemokine receptor type 5 (CCR5) is the major coreceptor used by HIV-1 to infect T cells, macrophages, and other cell types. Individuals who are heterozygous or homozy-gous for the CCR5Δ32 mutation in the CCR5 gene have slower progression or resistance to HIV infections, respectively (1–3). One patient has apparently been cured of HIV infection follow-ing allogeneic hematopoietic stem cell transplants from a homo-zygous CCR5Δ32 donor (4). This finding suggests a promising avenue for developing stem cell therapy to treat HIV infection. However, although it is encouraging, allogeneic transplantation is not likely to be widely applicable because the low frequency of CCR5Δ32 homozygotes in the general population plus the lo-gistics and feasibility of identifying suitable HLA-compatible donors with this mutation hinder practical applications. Further-more, this approach requires full bone marrow ablation and im-mune suppression. Autologous transplantations are less toxic, because they may not require complete bone marrow ablation or immune sup-pression for engraftment. In this setting, several studies have attempted to produce HIV resistance by disabling the CCR5 gene in CD34 + hematopoietic stem progenitor cells (HSPCs) or CD4 + T cells using shRNA or by gene disruption using zinc
Proceedings of the National Academy of Sciences 06/2014; 111(26):9591-9596. · 9.81 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To describe the observed characteristics of first prenatal visit breastfeeding discussions between obstetric providers and their pregnant patients.
This analysis was part of a larger study involving 69 health care providers and 377 patients attending their initial prenatal visits at a single clinic. Audio recordings and transcripts from the first 172 visits (including 36 obstetric-gynecology residents, six nurse midwives, and five nurse practitioners) were reviewed for breastfeeding discussion occurrence, timing and initiator of discussions, and adherence to American College of Obstetricians and Gynecologists (College) prenatal breastfeeding guidelines. Descriptive statistics were used to characterize the sample and frequency of breastfeeding discussions. Logistic regression and χ tests were used to examine patterns in women's breastfeeding discussion preferences and discussion occurrence. Conversations were qualitatively analyzed for breastfeeding content.
Breastfeeding discussions were infrequent (29% of visits), brief (mean 39 seconds), and most often initiated by clinicians in an ambivalent manner. Sixty-nine percent of breastfeeding discussions incorporated any College breastfeeding recommendations. Breastfeeding was significantly more likely to be discussed by certified nurse midwives than residents (odds ratio 24.54, 95% confidence interval 3.78-159.06; P<.01), and certified nurse midwives tended to engage patients in more open discussions. Women indicating a preference for breastfeeding discussions at the first visit (n=19) were more likely to actually have the discussion (P<.001).
Observed breastfeeding education at the first prenatal visit was suboptimal. The causes and effect of this deficiency on breastfeeding outcomes remains an important point of investigation. LEVEL OF EVIDENCE:: II.
Obstetrics and Gynecology 11/2013; · 4.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose: To qualitatively explore whether and how providers communicate pregnancy-related risks to patients during their first prenatal care visits.
Methods: We conducted a secondary analysis of 145 transcribed initial prenatal care visits in order to quantify and contextualize discussions of risk during prenatal assessments. Two investigators (BTE, FM) independently applied open codes to all instances where providers mentioned the word “risk”, identifying the context and content of the conversation. Codes were then organized and collapsed into thematic categories. NVivo 10 facilitated qualitative analysis.
Results: Obstetric providers mentioned the word “risk” 510 times in 110 of the 145 audio-recorded visits (mean = 4.8 times/visit; range = 1-17). Providers primarily discussed risk in the context of fetal chromosomal abnormalities (e.g. Down Syndrome). Risk was also readily discussed in regards to patients’ obstetrical and social histories (e.g. prior preterm delivery, gestational diabetes, depression, smoking or substance abuse). Messages about risk were more often framed in regards to risk to the fetus, with less attention to potential risks to the mother. Maternal risks were usually discussed in the context of three overarching categories: medical risks, obstetrical risks, and social or behavioral risk. Numerical descriptions of risk were utilized often. Final analyses will identify the relative frequency and salience of risk categorizations.
Conclusion: Reports of underutilization of prenatal care among ‘high-risk’ patients may reflect an incongruency in patients’ risk perceptions and providers’ risk assessments. We found that obstetric providers primarily talk to patients about risk in the context of genetic and inherited disorders. It is possible that because this constitutes theoretical risk rather than personal risk, this diminishes the sense in a patient that she indeed is a ‘high-risk’ patient. Furthermore, providers tended to discuss risks that can be modified through behavior change or medical intervention (e.g. smoking cessation or genetic testing). Providers may be more inclined to discuss risk factors that can be addressed by a clear course of action; while failing to convey other important risk-factors or concerns to patients. This study is a first step in understanding the nature of prenatal risk-communication and physician disclosure about pregnancy-related risks. Further research is needed to assess the effectiveness of providers’ risk-communication by exploring patients’ risk perceptions in relation to risk assessments provided during prenatal consultations.
The 35th Annual Meeting of the Society for Medical Decision Making; 10/2013
[Show abstract][Hide abstract] ABSTRACT: Abstract Purpose. To use direct observations of first prenatal visits to describe obstetric providers' adherence to the evidence-based clinical practice guideline for smoking cessation counseling recommended by the American College of Obstetricians and Gynecologists, the 5 A's (Ask, Advice, Assess, Assist, and Arrange). Design. Observational study using audio recordings of first obstetric visits. Setting. An urban academic hospital-based clinic. Participants. Obstetric care providers and pregnant women attending their first obstetric visit. Method. First obstetric visits were audio recorded. Visits were identified in which patients reported smoking, and discussions were analyzed for obstetric providers' use of the 5 A's in smoking cessation counseling. Results. Obstetric providers asked about smoking in 98% of the 116 visits analyzed, but used 3 or more of the 5 A's in only 21% (24) of visits. In no visits did providers use all 5 A's. In 54% of the visits, providers gave patients information about smoking, most commonly about risks associated with perinatal smoking. Conclusion. Few obstetric care providers performed the recommended 5 A's smoking cessation counseling with their pregnant smokers. Effective and innovative methods are needed to improve obstetric providers' use of the 5 A's.
American journal of health promotion: AJHP 01/2013; 27(3):170-6. · 2.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Training in intimate partner violence (IPV) improves health professionals' knowledge and comfort regarding IPV; the optimal training frequency and format is unknown. We assessed how various types and amounts of IPV education for medical students affected knowledge and attitudes. Medical students at a large, urban university completed a survey concerning IPV-related knowledge and attitudes and participation in didactic and experiential IPV training activities. This was a one-time assessment. Of 586 students, 279 (48%) completed the survey. IPV-related knowledge increased with increased number of training activities. Knowledge and attitude scores were higher (p < .001) for respondents with experiential, versus only didactic, activities.
Violence Against Women 10/2012; · 1.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To compare in person versus computerized screening for intimate partner violence (IPV) in a hospital-based prenatal clinic and explore women's assessment of the screening methods.
We compared patient IPV disclosures on a computerized questionnaire to audio-taped first obstetric visits with an obstetric care provider and performed semi-structured interviews with patient participants who reported experiencing IPV.
Two-hundred and fifty patient participants and 52 provider participants were in the study. Ninety-one (36%) patients disclosed IPV either via computer or in person. Of those who disclosed IPV, 60 (66%) disclosed via both methods, but 31 (34%) disclosed IPV via only one of the two methods. Twenty-three women returned for interviews. They recommended using both types together. While computerized screening was felt to be non-judgmental and more anonymous, in person screening allowed for tailored questioning and more emotional connection with the provider.
Computerized screening allowed disclosure without fear of immediate judgment. In person screening allows more flexibility in wording of questions regarding IPV and opportunity for interpersonal rapport.
Both computerized or self-completed screening and in person screening is recommended. Providers should address IPV using non-judgmental, descriptive language, include assessments for psychological IPV, and repeat screening in person, even if no patient disclosure occurs via computer.
Patient Education and Counseling 07/2012; 88(3):443-8. · 2.60 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The objective of the authors in this study was to identify pregnant, low-income African American women's barriers and facilitators to exercise during pregnancy. A series of six focus groups with pregnant African American women were audio-recorded and transcribed verbatim. Focus group transcripts were qualitatively analyzed for major themes and independently coded for barriers and facilitators to exercise during pregnancy. A total of 34 pregnant, African American women participated in six focus groups from June through October of 2007. The majority of women were single (94%), had only a high school education (67%), received Medicaid (100%) and had a mean body mass index of 33 kg/m(2). All participants believed that exercise was beneficial during their pregnancy. However, participants faced multiple barriers including: (1) individual, (2) information, (3) resource, and (4) socio-cultural. African American women also described two facilitators to increase exercise during pregnancy: (1) group exercise classes, and (2) increasing the number of safe, low-cost exercise facilities in their communities. African American women living in low socioeconomic communities face several barriers to exercise during pregnancy. Targeted interventions to overcome barriers and facilitate exercise for this patient population should focus on increasing education from providers regarding the type and frequency of exercise recommended during pregnancy, enhancing social support networks with group exercise programs, and providing affordable and convenient locations to exercise.
Women & Health 11/2011; 51(8):777-94. · 1.05 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: Identifying illicit drug use during pregnancy is the first step toward intervention and preventing the negative consequences of perinatal drug use. However, little is known about how obstetric care providers screen for illicit drug use and what methods of questionning elicits more disclosure.
Objective: To examine patient-provider illicit drug use screening conversations during the first obstetric visit.
Methods: Audio-recordings of patient-provider conversations during the first obstetric visit were qualitatively analyzed for drug screening questions; these questions were categorized by whether they were: 1) detailed (e.g. naming specific drugs), 2) general (e.g., "Any drugs?") and 3) if the provider asked about illicit drugs with more than one question.
Results: Two-hundred fifty patients and 56 obstetric care providers participated. In 224 visits (89.6%) providers screened for illicit drug use in some manner. Seventy-seven patients (31.7%) disclosed illicit drug use. Drug use disclosures were more likely when providers' screening was: 1) detailed (RR 2.12, 95% CI 1.57-3.04) and 2) repeated (RR 2.73, 95% CI 1.93-3.84). A provider asking about drug use using very general questioning was less likely to result in a patient's drug use disclosure (RR 0.39, 95% CI 0.28-0.55).
Conclusion: Identification of illicit drug use during pregnancy may increase if obstetric care providers use more detailed questions and repeated questioning to screen their pregnant patients.
139st APHA Annual Meeting and Exposition 2011; 11/2011
[Show abstract][Hide abstract] ABSTRACT: Objective: To describe obstetric providers' adherence to best practice smoking cessation guidelines. Methods: We audio recorded first obstetric visits, identified visits in which patients reported smoking, and analyzed discussions for obstetric providers' use of the 5 A's (Ask, Advice, Assess, Assist and Arrange) in smoking cessation counseling. Results: Although obstetric providers asked about smoking in 98% of the 116 visits analyzed, in only 24 (21%) of the visits did providers use 3 or more of the 5 A's. No visits had all 5 A's. In 54% of the visits, the provider gave the patient some type of information about smoking; most commonly, this was information about the risks associated with perinatal smoking. Conclusion: When directly observed, few obstetric care providers performed the recommended 5 A's smoking cessation counseling with their pregnant smokers. Effective and innovative methods are needed to improve obstetric providers' use of the 5 A's.
139st APHA Annual Meeting and Exposition 2011; 11/2011
[Show abstract][Hide abstract] ABSTRACT: Background: Illicit drug use during pregnancy is associated with negative pregnancy, infant and maternal outcomes. Past illicit drug use is a predictor of perinatal drug use. However, little is know whether obstetric care providers screen for past drug use during clinic visits. Objective: To examine patient-provider discussions during the first obstetric visit for screening of past drug use. Methods: First obstetric visits between obstetric care providers and pregnant patients were audio-recorded. Conversations were qualitatively analyzed for drug screening questions; these questions were then categorized by whether the provider specifically asked about past or present use. Results: Two-hundred fifty patients and 56 obstetric care providers participated. In 224 visits (89.6%) providers screened for illicit drug use in some manner. Providers asked specifically about current use in 78 visits (31.2%), and about past use in 60 visits (24.0%). In 143 (57.2%) visits, questioning about drug use did not specify past or current use (e.g., "Drugs?" or "Any drug use?"). Seventy-three patients (29.2%) disclosed illicit drug use. Patient disclosure of drug use was associated with questions specifying past (RR 3.30; 95% CI 2.34-4.63) or current (RR 1.99; 95% CI 1.40-2.85) use. Disclosure was less likely if the screening did not specify time of use (RR 0.34; 95% CI 0.23-0.51). Conclusion: A provider specifically asking about past and current drug use are both effective but underutilized techniques for identifying illicit drug use among pregnant patients. Providers who screen using general, nonspecific questions may be missing opportunities for intervention during the first obstetric visit.
139st APHA Annual Meeting and Exposition 2011; 11/2011
[Show abstract][Hide abstract] ABSTRACT: 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(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.
Maternal and Child Health Journal 09/2011; 16(6):1180-7. · 2.24 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Research addressing the impact of neighborhood factors on intimate partner violence (IPV) often lacks discussion of how and why such factors impact IPV. In order to address this gap, 16 prominent neighborhood individuals (PNI) from 4 low-income urban neighborhoods were asked to share through in-depth interviews their insights and perceptions of IPV as an issue in their neighborhoods, and the relationship between social and structural neighborhood-level factors and IPV. PNIs most often associated IPV with only physical violence. Several did not feel IPV was a significant issue in their neighborhood, confirming a lack of awareness and underreporting of IPV. However, other PNIs were able to speak of the relationship between IPV and neighborhood factors, including lack of opportunities for employment, vacant housing, trash management, lack of community awareness, and social capacity to act to address IPV. Results provide unique insights regarding the mechanisms linking neighborhood factors to IPV outcomes. These results contribute to a deeper understanding of contextual influences upon IPV, the development of tailored quantitative research and to the design of local multi-level public health IPV intervention and prevention efforts.
Journal of Urban Health 02/2011; 88(2):214-24. · 1.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To study a mental health sample to assess (1) the prevalence of physical, sexual and emotional intimate partner violence (IPV) victimization and perpetration, (2) the extent this sample reported being asked about IPV by mental health clinicians and (3) how prevalence and screening rates varied by gender.
Women and men receiving services at a large psychiatric facility completed anonymous written questionnaires.
A total of 524 adults were approached for study participation, and 428 (158 men, 270 women) completed a survey. Over half (51%) of participants experienced some form of IPV; 63% of women and 32% of men reported IPV victimization. Experience of IPV was more likely if participants were women and had diagnoses of posttraumatic stress disorder, anxiety disorder or bipolar disorder. Both women (33%) and men (16%) reported perpetrating IPV. The reported IPV screening rate by mental health providers was 44% for the whole sample (women: 55%; men: 27%).
IPV victimization and perpetration is a prevalent problem among women and men receiving mental health services. Clinicians are missing opportunities to screen for IPV as part of mental health evaluation and treatment.
General hospital psychiatry 01/2011; 33(1):58-65. · 2.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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 ΦC31 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.
Proceedings of the National Academy of Sciences 10/2010; 107(45):19467-72. · 9.81 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The article discusses a study conducted between December 2007 and March 2008 that involved 19 gender-stratified focus groups with African American parents and adolescents from Allegheny County, Pennsylvania, to explore the process and content of parent-adolescent communication about sex. Discussions about intimate partner violence (IPV) and healthy relationships emerge inductively as critical topics in these conversations. The authors use a grounded theory approach to content analysis to identify and organize themes related to discussions on these topics. A total of 125 participants from 52 families are recruited for the study. Family history of child sexual abuse often motivates discussions. Mothers are described as the primary parent discussing sexual issues with children. Fathers primarily role model ideal male partnership behavior for sons and daughters. Parents seek to prevent daughters from experiencing sexual abuse or emotional manipulation by partners and focus on instilling a sense of responsibility to and respect for romantic partners in sons. Parents prioritize and express the need for tools to influence their adolescent's socialization as romantic partners. Mothers and fathers approach this process differently. Family-focused interventions to prevent unhealthy relationships can build on parent's efforts.
Journal of Interpersonal Violence 10/2010; 26(11):2165-85. · 1.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Unplanned pregnancy is associated with psychosocial stress, post-partum depression, and future unplanned pregnancies. Our study describes how topics related to unplanned pregnancy were addressed with patients during the first prenatal visit.
We audio-recorded and transcribed initial prenatal visits between 48 patients and 16 providers from a clinic serving racially diverse, lower-socio-economic patients. We conducted a fine-grained thematic analysis of cases in which the patient's pregnancy was unplanned.
Of the 48 patients, 35 (73%) had unplanned pregnancies. Twenty-nine visits for unplanned pregnancies (83%) included discussion of the patient's feelings about the pregnancy. Approximately half (51%) of the visits touched on partner or other types of social support. Six patients (17%) were offered referrals to counseling or social services. Only four visits (11%) touched on future birth control options.
Most initial prenatal visits for unplanned pregnancies included discussion of patient feelings about the pregnancy. However, opportunities to discuss future birth control and for more in-depth follow-up regarding social support and psychological risks associated with unplanned pregnancy were typically missed.
Obstetrics care providers should be cautious about making assumptions and should consider discussing pregnancy circumstances and psychosocial issues in more depth when treating patients facing unplanned pregnancy.
Patient Education and Counseling 09/2010; 81(3):462-7. · 2.60 Impact Factor