Motivational Interviewing with Computer Assistance as an Intervention to Empower Women to Make Contraceptive Choices while Incarcerated: Study Protocol for Randomized Controlled Trial

Background: Unplanned pregnancies and sexually transmitted infections (STIs) are important and costly public health problems in the United States resulting from unprotected sexual intercourse. Risk factors for unplanned pregnancies and STIs (poverty, low educational attainment, homelessness, substance abuse, lack of health insurance, history of an abusive environment, and practice of commercial sex work) are especially high among women with a history of incarceration. Project CARE (Contraceptive Awareness and Reproductive Education) is designed to evaluate an innovative intervention, Motivational Interviewing with Computer Assistance (MICA), aimed at enhancing contraceptive initiation and maintenance among incarcerated women who do not want a pregnancy within the next year and who are anticipated to be released back to the community. This study aims to: (1) increase the initiation of highly effective contraceptives while incarcerated; (2) increase the continuation of highly effective contraceptive use at 3, 6, 9, and 12 months after release; and (3) decrease unsafe sexual activity. Methods/Design: This randomized controlled trial will recruit 400 women from the Rhode Island Department of Corrections (RI DOC) women’s jail at risk for an unplanned pregnancy (that is, sexually active with men and not planning/wanting to become pregnant in the next year). They will be randomized to two interventions: a control group who receive two educational videos (on contraception, STIs, and pre-conception counseling) or a treatment group who receive two sessions of personalized MICA. MICA is based on the principles of the Transtheoretical Model (TTM) and on Motivational Interviewing (MI), an empirically supported counseling technique designed to enhance readiness to change targeted behaviors. Women will be followed at 3, 6, 9, and 12 months post release and assessed for STIs, pregnancy, and reported condom use. Discussion: Results from this study are expected to enhance our understanding of the efficacy of MICA to enhance contraceptive initiation and maintenance and reduce sexual risk-taking behaviors among incarcerated women who have re-entered the community

A Randomized Controlled Trial to Compare Computer-assisted Motivational Intervention with Didactic Educational Counseling to Reduce Unprotected Sex in Female Adolescents

Study Objective: To examine a computer-assisted, counselor-guided motivational intervention (CAMI) aimed at reducing the risk of unprotected sexual intercourse. Design, Setting, Participants, Interventions, and Main Outcome Measures: We conducted a 9-month, longitudinal randomized controlled trial with a multisite recruitment strategy including clinic, university, and social referrals, and compared the CAMI with didactic educational counseling in 572 female adolescents with a mean age of 17 years (SD = 2.2 years; range = 13-21 years; 59% African American) who were at risk for pregnancy and sexually transmitted diseases. The primary outcome was the acceptability of the CAMI according to self-reported rating scales. The secondary outcome was the reduction of pregnancy and sexually transmitted disease risk using a 9-month, self-report timeline follow-back calendar of unprotected sex. Results: We conducted a 9-month, longitudinal randomized controlled trial with a multisite recruitment strategy including clinic, university, and social referrals, and compared the CAMI with didactic educational counseling in 572 female adolescents with a mean age of 17 years (SD = 2.2 years; range = 13-21 years; 59% African American) who were at risk for pregnancy and sexually transmitted diseases. The primary outcome was the acceptability of the CAMI according to self-reported rating scales. The secondary outcome was the reduction of pregnancy and sexually transmitted disease risk using a 9-month, self-report timeline follow-back calendar of unprotected sex. Conclusion: Among those who completed the intervention, the CAMI reduced unprotected sex among an at-risk, predominantly minority sample of female adolescents. Modification of the CAMI to address methodological issues that contributed to a high drop-out rate are needed to make the intervention more acceptable and feasible for use among sexually active predominantly minority, at-risk, female adolescents

A Qualitative Study of Rural Black Adolescents’ Perspectives on Primary STD Prevention Strategies

Primary STD prevention relies on five key strategies: practicing abstinence, choosing low-risk partners, discussing partners’ sexual history, using condoms consistently and not having multiple partners. Few studies have examined all of these strategies simultaneously, and few have focused on rural black adolescents, whose rates of early sexual initiation and STDs are among the highest in the nation

Poor Reporting of Scientific Leadership Information in Clinical Trial Registers

BACKGROUND: In September 2004, the International Committee of Medical Journal Editors (ICMJE) issued a Statement requiring that all clinical trials be registered at inception in a public register in order to be considered for publication. The World Health Organization (WHO) and ICMJE have identified 20 items that should be provided before a trial is considered registered, including contact information. Identifying those scientifically responsible for trial conduct increases accountability. The objective is to examine the proportion of registered clinical trials providing valid scientific leadership information. METHODOLOGY/PRINCIPAL FINDINGS: We reviewed clinical trial entries listing Canadian investigators in the two largest international and public trial registers, the International Standard Randomized Controlled Trial Number (ISRCTN) register, and ClinicalTrials.gov. The main outcome measures were the proportion of clinical trials reporting valid contact information for the trials' Principal Investigator (PI)/Co-ordinating Investigator/Study Chair/Site PI, and trial e-mail contact address, stratified by funding source, recruiting status, and register. A total of 1388 entries (142 from ISRCTN and 1246 from ClinicalTrials.gov) comprised our sample. We found non-compliance with mandatory registration requirements regarding scientific leadership and trial contact information. Non-industry and partial industry funded trials were significantly more likely to identify the individual responsible for scientific leadership (OR = 259, 95% CI: 95-701) and to provide a contact e-mail address (OR = 9.6, 95% CI: 6.6-14) than were solely industry funded trials. CONCLUSIONS/SIGNIFICANCE: Despite the requirements set by WHO and ICMJE, data on scientific leadership and contact e-mail addresses are frequently omitted from clinical trials registered in the two leading public clinical trial registers. To promote accountability and transparency in clinical trials research, public clinical trials registers should ensure adequate monitoring of trial registration to ensure completion of mandatory contact information fields identifying scientific leadership

Variation in Sexual Behaviors in a Cohort of Adolescent Females: The Role of Personal, Perceived Peer, and Perceived Family Attitudes

Little is known about how adolescent sexual behaviors develop and the influence of personal or perceived social attitudes. We sought to describe how personal, perceived peer and perceived family attitudes towards adolescent sexual activity influences adolescent females’ sexual behaviors over time

Multi-omic association study identifies DNA methylation-mediated genotype and smoking exposure effects on lung function in children living in urban settings

Impaired lung function in early life is associated with the subsequent development of chronic respiratory disease. Most genetic associations with lung function have been identified in adults of European descent and therefore may not represent those most relevant to pediatric populations and populations of different ancestries. In this study, we performed genome-wide association analyses of lung function in a multiethnic cohort of children (n = 1,035) living in low-income urban neighborhoods. We identified one novel locus at the TDRD9 gene in chromosome 14q32.33 associated with percent predicted forced expiratory volume in one second (FEV1) (p = 2.4x10-9; βz = -0.31, 95% CI = -0.41- -0.21). Mendelian randomization and mediation analyses revealed that this genetic effect on FEV1 was partially mediated by DNA methylation levels at this locus in airway epithelial cells, which were also associated with environmental tobacco smoke exposure (p = 0.015). Promoter-enhancer interactions in airway epithelial cells revealed chromatin interaction loops between FEV1-associated variants in TDRD9 and the promoter region of the PPP1R13B gene, a stimulator of p53-mediated apoptosis. Expression of PPP1R13B in airway epithelial cells was significantly associated the FEV1 risk alleles (p = 1.3x10-5; β = 0.12, 95% CI = 0.06–0.17). These combined results highlight a potential novel mechanism for reduced lung function in urban youth resulting from both genetics and smoking exposure

Human mucosal associated invariant T cells detect bacterially infected cells

Control of infection with Mycobacterium tuberculosis (Mtb) requires Th1-type immunity, of which CD8+ T cells play a unique role. High frequency Mtb-reactive CD8+ T cells are present in both Mtb-infected and uninfected humans. We show by limiting dilution analysis that nonclassically restricted CD8+ T cells are universally present, but predominate in Mtbuninfected individuals. Interestingly, these Mtb-reactive cells expressed the Va7.2 T-cell receptor (TCR), were restricted by the nonclassical MHC (HLA-Ib) molecule MR1, and were activated in a transporter associated with antigen processing and presentation (TAP) independent manner. These properties are all characteristics of mucosal associated invariant T cells (MAIT), an "innate" T-cell population of previously unknown function. These MAIT cells also detect cells infected with other bacteria. Direct ex vivo analysis demonstrates that Mtb-reactive MAIT cells are decreased in peripheral blood mononuclear cells (PBMCs) from individuals with active tuberculosis, are enriched in human lung, and respond to Mtb-infected MR1-expressing lung epithelial cells. Overall, these findings suggest a generalized role for MAIT cells in the detection of bacterially infected cells, and potentially in the control of bacterial infection. © 2010 Gold et al

Endosomal MR1 Trafficking Plays a Key Role in Presentation of Mycobacterium tuberculosis Ligands to MAIT Cells

Mucosal-Associated Invariant T (MAIT) cells, present in high frequency in airway and other mucosal tissues, have Th1 effector capacity positioning them to play a critical role in the early immune response to intracellular pathogens, including Mycobacterium tuberculosis (Mtb). MR1 is a highly conserved Class I-like molecule that presents vitamin B metabolites to MAIT cells. The mechanisms for loading these ubiquitous small molecules are likely to be tightly regulated to prevent inappropriate MAIT cell activation. To define the intracellular localization of MR1, we analyzed the distribution of an MR1-GFP fusion protein in antigen presenting cells. We found that MR1 localized to endosomes and was translocated to the cell surface upon addition of 6-formyl pterin (6-FP). To understand the mechanisms by which MR1 antigens are presented, we used a lentiviral shRNA screen to identify trafficking molecules that are required for the presentation of Mtb antigen to HLA-diverse T cells. We identified Stx18, VAMP4, and Rab6 as trafficking molecules regulating MR1-dependent MAIT cell recognition of Mtb-infected cells. Stx18 but not VAMP4 or Rab6 knockdown also resulted in decreased 6-FP-dependent surface translocation of MR1 suggesting distinct pathways for loading of exogenous ligands and intracellular mycobacterially-derived ligands. We postulate that endosome-mediated trafficking of MR1 allows for selective sampling of the intracellular environment.Career Development Award: (#IK2 CX000538); U.S. Department of Veterans Affairs Clinical Sciences Research and Development Program (MJH); U.S.Department of Veterans Affairs Biomedical Laboratory Research and Development Program (DML) Merit Award: (#I01 BX000533); American Lung Association: (RT-350058)

Maternal autoimmunity and inflammation are associated with childhood tics and obsessive-compulsive disorder: Transcriptomic data show common enriched innate immune pathways.

Although genetic variation is a major risk factor of neurodevelopmental disorders, environmental factors during pregnancy and early life are also important in disease expression. Animal models demonstrate that maternal inflammation causes fetal neuroinflammation and neurodevelopmental deficits, and brain transcriptomics of neurodevelopmental disorders in humans show upregulated differentially expressed genes are enriched in immune pathways. We prospectively recruited 200 sequentially referred children with tic disorders/obsessive-compulsive disorder (OCD), 100 autoimmune neurological controls, and 100 age-matched healthy controls. A structured interview captured the maternal and family history of autoimmune disease and other pro-inflammatory states. Maternal blood and published Tourette brain transcriptomes were analysed for overlapping enriched pathways. Mothers of children with tics/OCD had a higher rate of autoimmune disease compared with mothers of children with autoimmune neurological conditions (p = 0.054), and mothers of healthy controls (p = 0.0004). Autoimmunity was similarly elevated in first- and second-degree maternal relatives of children with tics/OCD (p 0.0001 and p = 0.014 respectively). Other pro-inflammatory states were also more common in mothers of children with tics/OCD than controls (p 0.0001). Upregulated differentially expressed genes in maternal autoimmune disease and Tourette brain transcriptomes were commonly enriched in innate immune processes. Pro-inflammatory states, including autoimmune disease, are more common in the mothers and families of children with tics/OCD. Exploratory transcriptome analysis indicates innate immune signalling may link maternal inflammation and childhood tics/OCD. Targeting inflammation may represent preventative strategies in pregnancy and treatment opportunities for children with neurodevelopmental disorders