Barriers to asymptomatic screening and other STD services for adolescents and young adults: focus group discussions

BACKGROUND: Sexually transmitted diseases (STDs) are a major public health problem among young people and can lead to the spread of HIV. Previous studies have primarily addressed barriers to STD care for symptomatic patients. The purpose of our study was to identify perceptions about existing barriers to and ideal services for STDs, especially asymptomatic screening, among young people in a southeastern community. METHODS: Eight focus group discussions including 53 White, African American, and Latino youth (age 14–24) were conducted. RESULTS: Perceived barriers to care included lack of knowledge of STDs and available services, cost, shame associated with seeking services, long clinic waiting times, discrimination, and urethral specimen collection methods. Perceived features of ideal STD services included locations close to familiar places, extended hours, and urine-based screening. Television was perceived as the most effective route of disseminating STD information. CONCLUSIONS: Further research is warranted to evaluate improving convenience, efficiency, and privacy of existing services; adding urine-based screening and new services closer to neighborhoods; and using mass media to disseminate STD information as strategies to increase STD screening

A Family of Diverse Kunitz Inhibitors from Echinococcus granulosus Potentially Involved in Host-Parasite Cross-Talk

The cestode Echinococcus granulosus, the agent of hydatidosis/echinococcosis, is remarkably well adapted to its definitive host. However, the molecular mechanisms underlying the successful establishment of larval worms (protoscoleces) in the dog duodenum are unknown. With the aim of identifying molecules participating in the E. granulosus-dog cross-talk, we surveyed the transcriptomes of protoscoleces and protoscoleces treated with pepsin at pH 2. This analysis identified a multigene family of secreted monodomain Kunitz proteins associated mostly with pepsin/H+-treated worms, suggesting that they play a role at the onset of infection. We present the relevant molecular features of eight members of the E. granulosus Kunitz family (EgKU-1 – EgKU-8). Although diverse, the family includes three pairs of close paralogs (EgKU-1/EgKU-4; EgKU-3/EgKU-8; EgKU-6/EgKU-7), which would be the products of recent gene duplications. In addition, we describe the purification of EgKU-1 and EgKU-8 from larval worms, and provide data indicating that some members of the family (notably, EgKU-3 and EgKU-8) are secreted by protoscoleces. Detailed kinetic studies with native EgKU-1 and EgKU-8 highlighted their functional diversity. Like most monodomain Kunitz proteins, EgKU-8 behaved as a slow, tight-binding inhibitor of serine proteases, with global inhibition constants (KI*) versus trypsins in the picomolar range. In sharp contrast, EgKU-1 did not inhibit any of the assayed peptidases. Interestingly, molecular modeling revealed structural elements associated with activity in Kunitz cation-channel blockers. We propose that this family of inhibitors has the potential to act at the E. granulosus-dog interface and interfere with host physiological processes at the initial stages of infection

Human Non-neutralizing HIV-1 Envelope Monoclonal Antibodies Limit the Number of Founder Viruses during SHIV Mucosal Infection in Rhesus Macaques

HIV-1 mucosal transmission begins with virus or virus-infected cells moving through mucus across mucosal epithelium to infect CD4+ T cells. Although broadly neutralizing antibodies (bnAbs) are the type of HIV-1 antibodies that are most likely protective, they are not induced with current vaccine candidates. In contrast, antibodies that do not neutralize primary HIV-1 strains in the TZM-bl infection assay are readily induced by current vaccine candidates and have also been implicated as secondary correlates of decreased HIV-1 risk in the RV144 vaccine efficacy trial. Here, we have studied the capacity of anti-Env monoclonal antibodies (mAbs) against either the immunodominant region of gp41 (7B2 IgG1), the first constant region of gp120 (A32 IgG1), or the third variable loop (V3) of gp120 (CH22 IgG1) to modulate in vivo rectal mucosal transmission of a high-dose simian-human immunodeficiency virus (SHIV-BaL) in rhesus macaques. 7B2 IgG1 or A32 IgG1, each containing mutations to enhance Fc function, was administered passively to rhesus macaques but afforded no protection against productive clinical infection while the positive control antibody CH22 IgG1 prevented infection in 4 of 6 animals. Enumeration of transmitted/founder (T/F) viruses revealed that passive infusion of each of the three antibodies significantly reduced the number of T/F genomes. Thus, some antibodies that bind HIV-1 Env but fail to neutralize virus in traditional neutralization assays may limit the number of T/F viruses involved in transmission without leading to enhancement of viral infection. For one of these mAbs, gp41 mAb 7B2, we provide the first co-crystal structure in complex with a common cyclical loop motif demonstrated to be critical for infection by other retroviruses

KLF17 empowers TGF-β/Smad signaling by targeting Smad3-dependent pathway to suppress tumor growth and metastasis during cancer progression.

Inhibition of tumor suppressive signaling is linked to cancer progression, metastasis and epithelial-mesenchymal transition (EMT). Transforming growth factor-β1 (TGF-β)/Smad signaling plays an important role in tumor suppression. Kruppel-like-factor 17 (KLF17) is a negative regulator of metastasis and EMT. However, underlying mechanisms leading to tumor suppressive and anti-metastatic function of KLF17 still remains unknown. Here, we show that KLF17 plays an integral role in potentiating TGF-β/Smad signaling via Smad3-dependent pathway to suppress tumor progression. Intriguingly, TGF-β/Smad3 signaling induces KLF17 expression, generating a positive feedback loop. TGF-β/Smad3-KLF17 loop is critical for anti-metastasis and tumor inhibition in cancer cells. Mechanistically, silencing KLF17 reduced Smad3-DNA complex formation on Smad binding element (SBE) and affects the expression of TGF-β/Smad target genes. Moreover, KLF17 alters Smad3 binding pattern on chromatin. KLF17 regulates TGF-β target genes that are Smad3-dependent. Smad3 and KLF17 physically interact with each other via KLF17 responsive elements/SBE region. Intriguingly, TGF-β stimulates the recruitment of KLF17 on chromatin to subsets of metastasis-associated genes. Functionally, depletion of KLF17 enhanced tumorigenic features in cancer cells. KLF17 is critical for full cytostatic function of TGF-β/Smad signaling. Clinically, KLF17 expression significantly decreases during advance HCC. KLF17 shows positive correlation with Smad3 levels in cancer samples. Our data shows that enhance KLF17 activity has important therapeutic implications for targeted-therapies aimed at TGF-β/Smad3 pathway. These findings define novel mechanism by which TGF-β/Smad-KLF17 pathway mutually affect each other during cancer metastasis, provide a new model of regulation of TGF-β/Smad signaling by KLF17 and defines new insights into anti-metastatic function of KLF17