Evaluating a Future-Oriented Positive Youth Development Intervention to Reduce Sexual Risk Among Highly Mobile Youth: Results and Challenges.

PURPOSE: Youth experiencing or at risk of experiencing homelessness need tailored prevention programming to prevent unplanned pregnancy and sexually transmitted infections. This study evaluated the efficacy of a small-group, future-oriented positive youth development (PYD) intervention to reduce sexual risk behaviors. METHOD: Youth aged 14-19 (n = 483) experiencing or at risk of experiencing homelessness were recruited at youth-serving agencies and in alternative schools. Each cohort enrolled was randomized either to a 10-session, 5-week group future-oriented intervention to support them in adopting health-promoting behaviors such as using contraception, including condom use (n = 244) or to a no-treatment condition where they received usual services/schooling (n = 239). We assessed at baseline and 3-month and 9-month follow-up (1) vaginal intercourse without consistent contraception use, (2) vaginal and anal intercourse without consistent condom use, and (3) sexual risk behaviors, including current (last 3 months) effective contraception use by females who did not report current use at baseline. RESULTS: There was no significant difference between treatment and control conditions for most outcomes. However, among females not currently using contraception at baseline, 34% in the treatment condition compared to 12.9% in the control condition reported using contraception in the 3 months before the 9-month survey, a statistically significant difference. DISCUSSION: This sexual risk reduction intervention, grounded in PYD theory and tailored to address the needs of marginalized groups of youth, demonstrated efficacy at increasing contraceptive uptake among females. The need for PYD interventions that can be delivered in a variety of nontraditional school and service settings are discussed.

AIM for Teen Moms: Social Support's Role in Contraception Use Among Young Mothers.

PURPOSE: Rapid repeat pregnancy is associated with negative outcomes for teen mothers and their offspring. Contraceptive use can reduce this risk. We explored the impact of AIM for Teen Moms, a future-oriented behavioral intervention, on emotional and tangible support and the influence of this support on the attitudes, intentions, and past 3-month contraceptive use behaviors. METHOD: Participants were 295 first-time moms (ages 15-19) in Los Angeles County who participated in a randomized control trial intervention to reduce rapid repeat pregnancies. Participants completed surveys at baseline and 36-months. Hypotheses were tested using multivariate and interaction analysis. RESULTS: Teen mothers in treatment group reported more emotional (ß =.13, p < .05) and tangible support (ß =.13, p < .05). Higher tangible support was positively associated with birth control attitudes (ß =.13, p < .05), which, in turn, predicted intention to use birth control (ß =.31, p < .001). Intention to use birth control also predicted higher past 3-month birth control use (ß =.18, p < .01); there was also a direct path from attitude to 3-month birth control use (ß =.35, p < .001). There was no association between emotional support and birth control attitudes, intentions, or behaviors. CONCLUSION: AIM for Teen Mom's effects on contraception use at 36 months was mediated by social support, specifically tangible support, which, in turn, affected birth control attitudes, intentions, and reported birth control use. Interventionists must consider how intervention content can specifically address the building of target support to meet the needs of teen mothers.

Antiretroviral Therapy Normalizes Autoantibody Profile of HIV Patients by Decreasing CD33⁺CD11b⁺HLA-DR⁺ Cells: A Cross-Sectional Study.

Autoimmune manifestations are common in human immunodeficiency virus (HIV) patients. However, the autoantibody spectrum associated with HIV infection and the impact of antiretroviral therapy (ART) remains to be determined. The plasma autoantibody spectrum for HIV patients was characterized by protein microarrays containing 83 autoantigens and confirmed by enzyme-linked immunosorbent assay (ELISA). Regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) were analyzed by flow cytometry and their effects on autoantibodies production were determined by B cell ELISpot. Higher levels of autoantibody and higher prevalence of elevated autoantibodies were observed in ART-naive HIV patients compared to healthy subjects and HIV patients on ART. The highest frequency of CD33(+)CD11b(+)HLA-DR(+) cells was observed in ART-naive HIV patients and was associated with the quantity of elevated autoantibodies. In addition, CD33(+)CD11b(+)HLA-DR(+) cells other than Tregs or MDSCs boost the B cell response in a dose-dependent manner by in vitro assay. In summary, HIV infection leads to elevation of autoantibodies while ART suppresses the autoimmune manifestation by decreasing CD33(+)CD11b(+)HLA-DR(+) cells in vivo.The roles of CD33(+)CD11b(+)HLA-DR(+) cells on disease progression in HIV patients needs further assessment.

Young men and the morning after: a missed opportunity for emergency contraception provision?

OBJECTIVES: Although adolescents and young adults of lower socioeconomic status (SES) are disproportionately affected by unintended pregnancies, research on experiences with emergency contraception (EC) in this population has lagged. Furthermore, it is unclear whether EC-related knowledge and behaviour varies between young men and women. This study investigated knowledge, attitudes and experiences with EC among low SES young men and women aged 18-25 years. METHODS: One hundred and ninety-eight new enrollees at two Los Angeles primary medical care clinics completed surveys about their knowledge, past use and likelihood of using EC. Chi square (χ(2)) and regression analyses assessed gender differences in knowledge and attitudes. RESULTS: Women were more likely than men to accurately answer questions about EC and its use. Across both sexes, accurate knowledge predicted future willingness to use EC. Only half the women and a third of men knew that EC could be directly dispensed by pharmacists; even fewer knew that the legal access age for EC was 17 years (13%) or that men could access EC from pharmacies for their female partners (24%). Although respondents most commonly reported that friends were their source of current information about EC, both men and women chose health care professionals as their desired source of future information about EC. CONCLUSIONS: Young men in this sample were significantly less knowledgeable than young women about EC. Educating young men about EC by health care providers during routine visits may be a unique opportunity to increase EC knowledge, access and use among low-income young couples to decrease undesired pregnancies.

Provirus activation plus CD59 blockage triggers antibody-dependent complement-mediated lysis of latently HIV-1-infected cells.

Latently HIV-1-infected cells are recognized as the last barrier toward viral eradication and cure. To purge these cells, we combined a provirus stimulant with a blocker of human CD59, a key member of the regulators of complement activation, to trigger Ab-dependent complement-mediated lysis. Provirus stimulants including prostratin and histone deacetylase inhibitors such as romidepsin and suberoylanilide hydroxamic acid activated proviruses in the latently HIV-1-infected T cell line ACH-2 as virion production and viral protein expression on the cell surface were induced. Romidepsin was the most attractive provirus stimulant as it effectively activated proviruses at nanomolar concentrations that can be achieved clinically. Antiretroviral drugs including two protease inhibitors (atazanavir and darunavir) and an RT inhibitor (emtricitabine) did not affect the activity of provirus stimulants in the activation of proviruses. However, saquinavir (a protease inhibitor) markedly suppressed virus production, although it did not affect the percentage of cells expressing viral Env on the cell surface. Provirus-activated ACH-2 cells expressed HIV-1 Env that colocalized with CD59 in lipid rafts on the cell surface, facilitating direct interaction between them. Blockage of CD59 rendered provirus-activated ACH-2 cells and primary human CD4(+) T cells that were latently infected with HIV-1 sensitive to Ab-dependent complement-mediated lysis by anti-HIV-1 polyclonal Abs or plasma from HIV-1-infected patients. Therefore, a combination of provirus stimulants with regulators of complement activation blockers represents a novel approach to eliminate HIV-1.

Primary human macrophages serve as vehicles for vaccinia virus replication and dissemination.

UNLABELLED: Human monocytic and professional antigen-presenting cells have been reported only to exhibit abortive infections with vaccinia virus (VACV). We found that monocyte-derived macrophages (MDMs), including granulocyte macrophage colony-stimulating factor (GM-CSF)-polarized M1 and macrophage colony-stimulating factor (M-CSF)-polarized M2, but not human AB serum-derived cells, were permissive to VACV replication. The titers of infectious virions in both cell-free supernatants and cellular lysates of infected M1 and M2 markedly increased in a time-dependent manner. The majority of virions produced in permissive MDMs were extracellular enveloped virions (EEV), a secreted form of VACV associated with long-range virus dissemination, and were mainly found in the culture supernatant. Infected MDMs formed VACV factories, actin tails, virion-associated branching structures, and cell linkages, indicating that MDMs are able to initiate de novo synthesis of viral DNA and promote virus release. VACV replication was sensitive to inhibitors against the Akt and Erk1/2 pathways that can be activated by VACV infection and M-CSF stimulation. Classical activation of MDMs by lipopolysaccharide (LPS) plus gamma interferon (IFN-γ) stimulation caused no effect on VACV replication, while alternative activation of MDMs by interleukin-10 (IL-10) or LPS-plus-IL-1ß treatment significantly decreased VACV production. The IL-10-mediated suppression of VACV replication was largely due to Stat3 activation, as a Stat3 inhibitor restored virus production to levels observed without IL-10 stimulation. In conclusion, our data demonstrate that primary human macrophages are permissive to VACV replication. After infection, these cells produce EEV for long-range dissemination and also form structures associated with virions which may contribute to cell-cell spread. IMPORTANCE: Our results provide critical information to the burgeoning fields of cancer-killing (oncolytic) virus therapy with vaccinia virus (VACV). One type of macrophage (M2) is considered a common presence in tumors and is associated with poor prognosis. Our results demonstrate a preference for VACV replication in M2 macrophages and could assist in designing treatments and engineering poxviruses with special considerations for their effect on M2 macrophage-containing tumors. Additionally, this work highlights the importance of macrophages in the field of vaccine development using poxviruses as vectors. The understanding of the dynamics of poxvirus-infected foci is central in understanding the effectiveness of the immune response to poxvirus-mediated vaccine vectors. Monocytic cells have been found to be an important part of VACV skin lesions in mice in controlling the infection as well as mediating virus transport out of infected foci.

HIV-1 coinfection profoundly alters intrahepatic chemokine but not inflammatory cytokine profiles in HCV-infected subjects.

UNLABELLED: The pathogenesis of accelerated liver damage in subjects coinfected with hepatitis C virus (HCV) and human immunodeficiency virus type 1 (HIV-1) remains largely unknown. Recent studies suggest that ongoing chronic liver inflammation is responsible for the liver injury in HCV-infected patients. We aimed to determine whether HIV-1 coinfection altered intrahepatic inflammatory profiles in HCV infection, thereby hastening liver damage. We used a real-time RT-PCR-based array to comparatively analyze intrahepatic inflammation gene profiles in liver biopsy specimens from HCV-infected (n = 16), HCV/HIV-1-coinfected (n = 8) and uninfected (n = 8) individuals. We then used human hepatocytes to study the molecular mechanisms underlying alternations of the inflammatory profiles. Compared with uninfected individuals, HCV infection and HCV/HIV-1 coinfection markedly altered expression of 59.5% and 50.0% of 84 inflammation-related genes tested, respectively. Among these genes affected, HCV infection up-regulated the expression of 24 genes and down-regulated the expression of 26 genes, whereas HCV/HIV-1 coinfection up-regulated the expression of 21 genes and down-regulated the expression of 21 genes. Compared with HCV infection, HCV/HIV-1 coinfection did not dramatically affect intrahepatic gene expression profiles of cytokines and their receptors, but profoundly altered expression of several chemokine genes including up-regulation of the CXCR3-associated chemokines. Human hepatocytes produced these chemokines in response to virus-related microbial translocation, viral protein stimulation, and antiviral immune responses. CONCLUSIONS: HIV-1 coinfection profoundly alters intrahepatic chemokine but not cytokine profiles in HCV-infected subjects. The altered chemokines may orchestrate the tissue-specific and cell-selective trafficking of immune cells and autoimmunity to accelerate liver disease in HCV/HIV-1 coinfection.

Coming of age on the streets: survival sex among homeless young women in Hollywood.

This study examined childhood physical or sexual abuse, involvement in dependency or delinquency systems, psychiatric hospitalization, and suicide as possible risk factors for survival sex among homeless young women. Homeless young women were found to have similarly high rates of childhood sexual abuse, dependency and delinquency systems involvement, and psychiatric hospitalization. Homeless young women involved in survival sex disclosed higher rates of attempted suicide and reported marginally higher rates of childhood physical abuse. Analysis of qualitative data showed that those engaged in survival sex were motivated primarily by desperation to meet basic needs including a place to stay, food and money, and one third mentioned that peers commonly were influential in decisions to engage in survival sex. Others were influenced by coercion (10%) or pursuit of drugs (10%). Young women engaged in survival sex generally experienced regret and shame about their experience.

Fragmented QRS on twelve-lead electrocardiogram predicts arrhythmic events in patients with ischemic and nonischemic cardiomyopathy.

BACKGROUND: Myocardial scar is a substrate for reentrant ventricular arrhythmias and is associated with poor prognosis. Fragmented QRS (fQRS) on 12-lead ECG represents myocardial conduction delays due to myocardial scar in patients with coronary artery disease (CAD). OBJECTIVE: The purpose of this study was to determine whether fQRS is associated with increased ventricular arrhythmic event and mortality in patients with CAD and nonischemic dilated cardiomyopathy (DCM). METHODS: Arrhythmic events and mortality were studied in 361 patients (91% male, age 63.3 +/- 11.4 years, mean follow-up 16.6 +/- 10.2 months) with CAD and DCM who received an implantable cardioverter-defibrillator for primary or secondary prophylaxis. fQRS included various RSR' patterns (QRS duration <120 ms), such as > or =1 R prime or notching of the R wave or S wave present on at least two contiguous leads of those representing anterior (V(1)-V(5)), lateral (I, aVL, V(6)), or inferior (II, III, aVF) myocardial segments. RESULTS: fQRS was present in 84 (23%) patients (fQRS group) and absent in 100 (28%) patients (non-fQRS group). Wide QRS (wQRS; QRS duration > or =120 ms) was present in 177 (49%) patients. Kaplan-Meier analysis revealed that event-free survival for an arrhythmic event (implantable cardioverter-defibrillator shock or antitachycardia pacing) was significantly lower in the fQRS group than in the non-fQRS and wQRS groups (P <.001 and P <.019, respectively). fQRS was an independent predictor of an arrhythmic event but not of death. CONCLUSION: fQRS on 12-lead ECG is a predictor of arrhythmic events in patients with CAD and DCM. fQRS is associated with a significantly decreased time to first arrhythmic event compared with non-fQRS and wQRS.

Promoting prenatal and early childhood health: evaluation of a statewide materials-based intervention for parents.

OBJECTIVES: There is a critical need for effective, large-scale health communication programs to support parents of children aged 0-5 years. We evaluated the effectiveness of the Kit for New Parents, a multimedia health and parenting resource now distributed annually to 500000 parents in California. METHODS: In this quasi-experimental study, 462 mothers in the intervention group and 1011 mothers in the comparison group, recruited from prenatal and postnatal programs, completed a baseline interview about health-relevant parenting knowledge, and mothers in the intervention group received the kit. Both groups were reinterviewed 2 months later. At 14-months postbaseline, 350 mothers in the intervention group and a sample of 414 mothers who had equivalent demographic characteristics (comparison group) were interviewed about parenting knowledge and practices. RESULTS: Of the mothers in the intervention group, 87% reported using the kit within 2 months after receiving it, and 53% had shared it with their partner. At both follow-ups, mothers in the intervention group showed greater gains in knowledge and reported better practices at 14 months than did mothers in the comparison group. Gains were greater for prenatal recipients and for Spanish speakers. Providers considered the kit a valuable resource for their parenting programs. CONCLUSIONS: The kit is an effective, low-cost, statewide health intervention for parents.