In vitro analysis of the invasive phenotype of SUM 149, an inflammatory breast cancer cell line

BACKGROUND: Inflammatory breast cancer (IBC) is the most lethal form of locally invasive breast cancer known. However, very little information is available on the cellular mechanisms responsible for manifestation of the IBC phenotype. To understand the unique phenotype of IBC, we compared the motile and adhesive interactions of an IBC cell line, SUM 149, to the non-IBC cell line SUM 102. RESULTS: Our results demonstrate that both IBC and non-IBC cell lines exhibit similar adhesive properties to basal lamina, but SUM 149 showed a marked increase in adhesion to collagen I. In vitro haptotaxis assays demonstrate that SUM 149 was less invasive, while wound healing assays show a less in vitro migratory phenotype for SUM 149 cells relative to SUM 102 cells. We also demonstrate a role for Rho and E-cadherin in the unique invasive phenotype of IBC. Immunoblotting reveals higher E-cadherin and RhoA expression in the IBC cell line but similar RhoC expression. Rhodamine phalloidin staining demonstrates increased formation of actin stress fibers and larger focal adhesions in SUM 149 relative to the SUM 102 cell line. CONCLUSION: The observed unique actin and cellular architecture as well as the invasive and adhesive responses to the extracellular matrix of SUM 149 IBC cells suggest that the preference of IBC cells for connective tissue, possibly a mediator important for the vasculogenic mimicry via tubulogenesis seen in IBC pathological specimens. Overexpression of E-cadherin and RhoA may contribute to passive dissemination of IBC by promoting cell-cell adhesion and actin cytoskeletal structures that maintain tissue integrity. Therefore, we believe that these findings indicate a passive metastatic mechanism by which IBC cells invade the circulatory system as tumor emboli rather than by active migratory mechanisms

Risky Sex and HIV Acquisition Among HIV Serodiscordant Couples in Zambia, 2002-2012: What Does Alcohol Have To Do With It?

In this paper we evaluate the effects of heavy alcohol consumption on sexual behavior, HIV acquisition, and antiretroviral treatment (ART) initiation in a longitudinal open cohort of 1929 serodiscordant couples in Lusaka, Zambia from 2002 to 2012. We evaluated factors associated with baseline heavy alcohol consumption and its association with condomless sex with the study partner, sex outside of the partnership, and ART initiation using multivariable logistic regression. We estimated the effect of alcohol consumption on HIV acquisition using multivariable Cox models. Baseline factors significantly associated with women's heavy drinking (drunk weekly or more in 12-months before enrollment) included woman's older age (adjusted prevalence odds ratio [aPOR] = 1.04), partner heavy drinking (aPOR = 3.93), and being HIV-infected (aPOR = 2.03). Heavy drinking among men was associated with less age disparity with partner (aPOR per year disparity = 0.97) and partner heavy drinking (aPOR = 1.63). Men's being drunk daily (aOR = 1.18), women's being drunk less than monthly (aOR = 1.39) vs. never drunk and being in a male HIV-negative and female HIV-positive union (aOR = 1.45) were associated with condomless sex. Heavy alcohol use was associated with having 1 or more outside sex partners among men (aOR drunk daily = 1.91, drunk weekly = 1.32, drunk monthly = 2.03 vs. never), and women (aOR drunk monthly = 2.75 vs. never). Being drunk weekly or more increased men's risk of HIV acquisition (adjusted hazard ratio [aHR] = 1.72). Men and women being drunk weekly or more was associated (p < 0.1) with women's seroconversion (aHR = 1.42 and aHR = 3.71 respectively). HIV-positive women who were drunk monthly or more had lower odds of initiating ART (aOR = 0.83; 95% CI = 0.70-0.99) adjusting for age, months since baseline and previous pregnancies. Individuals in HIV-serodiscordant couples who reported heavy drinking had more outside sex partnerships and condomless sex with their study partner and were more likely to acquire HIV. HIV-positive women had lower odds of initiating ART if they were heavy drinkers

Knowledge of HIV Serodiscordance, Transmission, and Prevention among Couples in Durban, South Africa

Objective Couples’ voluntary HIV counseling and testing (CVCT) significantly decreases HIV transmission within couples, the largest risk group in sub-Saharan Africa, but it is not currently offered in most HIV testing facilities. To roll out such an intervention, understanding locale-specific knowledge barriers is critical. In this study, we measured knowledge of HIV serodiscordance, transmission, and prevention before and after receipt of CVCT services in Durban. Design Pre- and post-CVCT knowledge surveys were administered to a selection of individuals seeking CVCT services. Methods Changes in knowledge scores were assessed with McNemar Chi-square tests for balanced data and generalized estimating equation methods for unbalanced data. Results The survey included 317 heterosexual black couples (634 individuals) who were primarily Zulu (87%), unemployed (47%), and had at least a secondary level education (78%). 28% of couples proved to be discordant. Only 30% of individuals thought serodiscordance between couples was possible pre‐CVCT compared to 95% post-CVCT. One-third thought there was at least one benefit of CVCT pre‐CVCT, increasing to 96% post‐CVCT. Overall, there were positive changes in knowledge about HIV transmission and prevention. However, many respondents thought all HIV positive mothers give birth to babies with AIDS (64% pre-CVCT, 59% post-CVCT) and that male circumcision does not protect negative men against HIV (70% pre-CVCT, 67% post-CVCT). Conclusions CVCT was well received and was followed by improvements in understanding of discordance, the benefits of joint testing, and HIV transmission. Country-level health messaging would benefit from targeting gaps in knowledge about serodiscordance, vertical transmission, and male circumcision

Implementation of Couples’ Voluntary HIV Counseling and Testing Services in Durban, South Africa

Background Couples’ voluntary HIV counseling and testing (CVCT) is an evidence-based intervention that significantly reduces HIV incidence in couples. Despite the high prevalence of HIV and HIV couple serodiscordance in South Africa, there are few CVCT services. Methods From February-June 2013, The Rwanda Zambia HIV Research Group provided support, training, and technical assistance for local counselors and promoters to pilot CVCT services in five hospital-based clinics in Durban, South Africa. Client-level data (age, gender, years cohabiting, pregnancy status, previous testing, antiretroviral treatment (ART) status, neighborhood, and test site) collected as a component of routine CVCT service operation is presented stratified by couple serostatus. Results Twenty counselors and 28 promoters completed training. Of 907 couples (1,814 individuals) that underwent CVCT, prevalence of HIV was 41.8 % and prevalence of HIV serodiscordance was 29.5 % (19.3 % M-F+, 10.3 % M + F-). Most participants were 25–34 years of age, and this group had the highest prevalence. Previous individual HIV testing was low (50 % for men, 63 % for women). Only 4 % of couples reported previous CVCT. Most (75 %) HIV+ partners were not on ART, and HIV+ individuals in discordant couples were more likely to be on ART than those in concordant positive couples. Pregnancy among HIV+ women was not associated with previous HIV testing or ART use. Conclusions Implementation of standard CVCT services was found to be feasible in Durban. The burden of HIV and couple serodiscordance in Durban was extremely high. CVCT would greatly benefit couples in Durban as an HIV prevention strategy

Factors Associated with Lifetime HIV Testing in Texas by Race/Ethnicity

Introduction: In United States, roughly 1/5 of all HIV infected persons remain undiagnosed. Because HIV testing is critical to improve prevention efforts, more research is needed to understand the characteristics of individuals who get tested for HIV. Methods: This secondary analysis of the 2010 Texas Behavioral Risk Factor Surveillance System used data from 9,744 respondents between 18-64 years of age to evaluate the relationship between demographic characteristics (gender, race/ethnicity, age, area of residence, education, marital status, employment status, and income), healthcare characteristics (insurance status, having a primary provider, and access to healthcare), and HIV risk behaviors with ever having received an HIV test. Results: Significant associations between gender, age, area of residence, marital and employment status, and HIV risk behaviors and HIV testing in a Texas population by race/ethnicity were observed. Conclusions: These findings have important implications for future research into racial/ethnic disparities between lifetime HIV testing, and can help guide practitioners who work with populations at risk for HIV/AIDS in Texas

Indeterminate and discrepant rapid HIV test results in couples' HIV testing and counselling centres in Africa

<p>Abstract</p> <p>Background</p> <p>Many HIV voluntary testing and counselling centres in Africa use rapid antibody tests, in parallel or in sequence, to establish same-day HIV status. The interpretation of indeterminate or discrepant results between different rapid tests on one sample poses a challenge. We investigated the use of an algorithm using three serial rapid HIV tests in cohabiting couples to resolve unclear serostatuses.</p> <p>Methods</p> <p>Heterosexual couples visited the Rwanda Zambia HIV Research Group testing centres in Kigali, Rwanda, and Lusaka, Zambia, to assess HIV infection status. Individuals with unclear HIV rapid antibody test results (indeterminate) or discrepant results were asked to return for repeat testing to resolve HIV status. If either partner of a couple tested positive or indeterminate with the screening test, both partners were tested with a confirmatory test. Individuals with indeterminate or discrepant results were further tested with a tie-breaker and monthly retesting. HIV-RNA viral load was determined when HIV status was not resolved by follow-up rapid testing. Individuals were classified based on two of three initial tests as "Positive", "Negative" or "Other". Follow-up testing and/or HIV-RNA viral load testing determined them as "Infected", "Uninfected" or "Unresolved".</p> <p>Results</p> <p>Of 45,820 individuals tested as couples, 2.3% (4.1% of couples) had at least one discrepant or indeterminate rapid result. A total of 65% of those individuals had follow-up testing and of those individuals initially classified as "Negative" by three initial rapid tests, less than 1% were resolved as "Infected". In contrast, of those individuals with at least one discrepant or indeterminate result who were initially classified as "Positive", only 46% were resolved as "Infected", while the remainder was resolved as "Uninfected" (46%) or "Unresolved" (8%). A positive HIV serostatus of one of the partners was a strong predictor of infection in the other partner as 48% of individuals who resolved as "Infected" had an HIV-infected spouse.</p> <p>Conclusions</p> <p>In more than 45,000 individuals counselled and tested as couples, only 5% of individuals with indeterminate or discrepant rapid HIV test results were HIV infected. This represented only 0.1% of all individuals tested. Thus, algorithms using screening, confirmatory and tie-breaker rapid tests are reliable with two of three tests negative, but not when two of three tests are positive. False positive antibody tests may persist. HIV-positive partner serostatus should prompt repeat testing.</p

Trends of and factors associated with live-birth and abortion rates among HIV-positive and HIV-negative women

Little is known about fertility choices and pregnancy outcome rates among HIV-infected women in the current combination ART era

A cluster randomized trial to reduce HIV risk from outside partnerships in Zambian HIV-Negative couples using a novel behavioral intervention, "Strengthening Our Vows": Study protocol and baseline data.

BACKGROUND: Heterosexual couples contribute to most new HIV infections in areas of generalized HIV epidemics in sub-Saharan Africa. After Couples' Voluntary HIV Counseling and Testing (CVCT), heterosexual concordant HIV negative couples (CNC) in cohabiting unions contribute to approximately 47% of residual new infections in couples. These infections are attributed to concurrent sexual partners, a key driver of the HIV epidemic in Zambia. METHODS/DESIGN: Ten Zambian government clinics in two of the largest cities were randomized in matched pairs to a Strengthening Our Vows (SOV) intervention or a Good Health Package (GHP) comparison arm. SOV addressed preventing HIV infection from concurrent partners and protecting spouses after exposures outside the relationship. GHP focused on handwashing; water chlorination; household deworming; and screening for hypertension, diabetes and schistosomiasis. CNC were referred from CVCT services in government clinics. Follow-up includes post-intervention questionnaires and outcome assessments through 60 months. Longitudinal outcomes of interest include self-report and laboratory markers of condomless sex with outside partners and reported sexual agreements. We present baseline characteristics and factors associated with study arm and reported risk using descriptive statistics. RESULTS: The mean age of men was 32 and 26 for women. On average, couples cohabited for 6 years and had 2 children. Baseline analyses demonstrated some failures of randomization by study arm which will be considered in future primary analyses of longitudinal data. An HIV/STI risk factor composite was not different in the two study arms. Almost one-quarter of couples had an HIV risk factor at baseline. DISCUSSION: In preparation for future biomedical and behavioral interventions in sub-Saharan Africa, it is critical to understand and decrease HIV risk within CNC

Review for the generalist: evaluation of anterior knee pain

Anterior knee pain is common in children and adolescents. Evaluation and management is challenging and requires a thorough history and physical exam, and understanding of the pediatric skeleton. This article will review common causes of chronic anterior knee pain in the pediatric population with a focus on patellofemoral pain

Uptake of long acting reversible contraception following integrated couples HIV and fertility goal-based family planning counselling in Catholic and non-Catholic, urban and rural government health centers in Kigali, Rwanda.

BACKGROUND: When integrated with couples' voluntary HIV counselling and testing (CVCT), family planning including long acting reversible contraceptives (LARC) addresses prongs one and two of prevention of mother-to-child transmission (PMTCT). METHODS: In this observational study, we enrolled equal numbers of HIV concordant and discordant couples in four rural and four urban clinics, with two Catholic and two non-Catholic clinics in each area. Eligible couples were fertile, not already using a LARC method, and wished to limit or delay fertility for at least 2 years. We provided CVCT and fertility goal-based family planning counselling with the offer of LARC and conducted multivariate analysis of clinic, couple, and individual predictors of LARC uptake. RESULTS: Of 1290 couples enrolled, 960 (74%) selected LARC: Jadelle 5-year implant (37%), Implanon 3-year implant (26%), or copper intrauterine device (IUD) (11%). Uptake was higher in non-Catholic clinics (85% vs. 63% in Catholic clinics, p < 0.0001), in urban clinics (82% vs. 67% in rural clinics, p < 0.0001), and in HIV concordant couples (79% vs. 70% of discordant couples, p = .0005). Religion of the couple was unrelated to clinic religious affiliation, and uptake was highest among Catholics (80%) and lowest among Protestants (70%) who were predominantly Pentecostal. In multivariable analysis, urban location and non-Catholic clinic affiliation, Catholic religion of woman or couple, younger age of men, lower educational level of both partners, non-use of condoms or injectable contraception at enrollment, prior discussion of LARC by the couple, and women not having concerns about negative side effects of implant were associated with LARC uptake. CONCLUSIONS: Fertility goal-based LARC recommendations combined with couples' HIV counselling and testing resulted in a high uptake of LARC methods, even among discordant couples using condoms for HIV prevention, in Catholic clinics, and in rural populations. This model successfully integrates prevention of HIV and unplanned pregnancy