How do young men narrate the redemption story of a sexual assault perpetrator?

Little is known about how young men who have committed sexual assault might acknowledge wrongdoing and eventually change and make amends. There are practical barriers to seeking the real redemption stories of perpetrators. To explore hypothetical pathways to young men's accountability-taking and amends (i.

Establishing baseline framework for hepatitis B virus micro-elimination in Ho Chi Minh City, Vietnam - A community-based seroprevalence study.

Background: We conducted a community-based seroprevalence study using three HBV seromarkers (HBsAg, anti-HBs, anti-HBc) in Ho Chi Minh City (HCMC), Vietnam, to (1) determine the prevalence of HBV serologic profiles; (2) document factors associated with HBV infection or susceptibility; and (3) propose strategies toward HBV elimination by 2030.

Methods: During 2019-2020, we deployed a multistage cluster design with probability proportionate to size, to recruit 20,000 adults for an HBV screening and linkage to care program citywide. Screening results with interpretation, recommendations, and health education materials were returned to participants.

Demonstration of a population-based HCV serosurvey in Ho Chi Minh City, Viet Nam: Establishing baseline prevalence of and continuum of care for HCV micro-elimination by 2030.

Background: A baseline of hepatitis C virus (HCV) burden and other HCV epidemiological profiles is necessary for HCV micro-elimination in Ho Chi Minh City (HCMC), Viet Nam. This study aimed to determine HCV exposure and prevalence of HCV viremia as well as the proportion of HCV testing and treatment uptake among participants.

Methods: From 2019 to 2020, the probability proportionate to size sampling method was deployed to representatively invite approximately 20,000 adults (18 or older) throughout HCMC to free screening and linkage to care for HCV.

Progressive Scale-up of HBV AND HCV Testing for Hepatitis Elimination in Vietnam.

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Unmet needs in occupational health: prevention and management of viral hepatitis in healthcare workers in Ho Chi Minh City, Vietnam: a mixed-methods study.

Objectives: Vietnam is an endemic area for hepatitis B virus and hepatitis C virus infection (HBV-HCV), yet its largest city, Ho Chi Minh City (HCMC), has no comprehensive policy to educate, screen, treat and protect healthcare workers (HCWs) from viral hepatitis. We conducted a mixed-methods study to document HBV-HCV infection rates, risk factors, local barriers and opportunities for providing education, screening and medical care for HCWs.

Design: This mixed-methods study involved an HBV and HCV serological evaluation, knowledge, attitude and practice survey about viral hepatitis and many in-depth interviews.

mRNA vaccination boosts cross-variant neutralizing antibodies elicited by SARS-CoV-2 infection.

Emerging SARS-CoV-2 variants have raised concerns about resistance to neutralizing antibodies elicited by previous infection or vaccination. We examined whether sera from recovered and naïve donors collected prior to, and following immunizations with existing mRNA vaccines, could neutralize the Wuhan-Hu-1 and B.1.

A single mRNA immunization boosts cross-variant neutralizing antibodies elicited by SARS-CoV-2 infection.

Emerging SARS-CoV-2 variants have raised concerns about resistance to neutralizing antibodies elicited by previous infection or vaccination. We examined whether sera from recovered and naive donors collected prior to, and following immunizations with existing mRNA vaccines, could neutralize the Wuhan-Hu-1 and B.1.

Recombinant HIV-1 vaccine candidates based on replication-defective flavivirus vector.

Multiple approaches utilizing viral and DNA vectors have shown promise in the development of an effective vaccine against HIV. In this study, an alternative replication-defective flavivirus vector, RepliVax (RV), was evaluated for the delivery of HIV-1 immunogens. Recombinant RV-HIV viruses were engineered to stably express clade C virus Gag and Env (gp120TM) proteins and propagated in Vero helper cells.

Neutralization Takes Precedence Over IgG or IgA Isotype-related Functions in Mucosal HIV-1 Antibody-mediated Protection.

HIV-1 infection occurs primarily through mucosal transmission. Application of biologically relevant mucosal models can advance understanding of the functional properties of antibodies that mediate HIV protection, thereby guiding antibody-based vaccine development. Here, we employed a human ex vivo vaginal HIV-1 infection model and a rhesus macaque in vivo intrarectal SHIV challenge model to probe the protective capacity of monoclonal broadly-neutralizing (bnAb) and non-neutralizing Abs (nnAbs) that were functionally modified by isotype switching.

In men at risk of HIV infection, IgM, IgG1, IgG3, and IgA reach the human foreskin epidermis.

We profiled the humoral response in the penis, an area that has been minimally explored but may be relevant for protecting insertive men against HIV and other sexually acquired infections. Comparing paired tissue samples from 20 men at risk of HIV infection, foreskin contains less immunoglobulin A (IgA) and more IgG2 than colon. Using foreskin dermal and epidermal explants and paired plasma from 17 men, we examined Ig accumulation by normalizing Ig to human serum albumin (HSA) transudation.

Development of a Minor Histocompatibility Antigen Vaccine Regimen in the Canine Model of Hematopoietic Cell Transplantation.

Background: Minor histocompatibility antigen (miHA) vaccines have the potential to augment graft-versus-tumor effects without graft-versus-host disease (GVHD). We used mixed hematopoietic chimerism in the canine model of major histocompatibility complex-matched allogeneic hematopoietic cell transplantation as a platform to develop a miHA vaccination regimen.

Methods: We engineered DNA plasmids and replication-deficient human adenovirus type 5 constructs encoding large sections of canine SMCY and the entire canine SRY gene.

Measuring inhibition of HIV replication by ex vivo CD8⁺ T cells.

HIV replication is unrestrained in vivo in the vast majority of infected subjects, and the ability of some rare individuals to control this virus is poorly understood. Standard immunogenicity assays for detecting HIV-1-specific CD8(+) T-cell responses, such as IFN-γ ELISpot and intracellular cytokine staining, generally fail to correlate with in vivo inhibition of HIV replication. Several viral inhibition assays, which measure the effectiveness of CD8(+) T-cell responses in suppressing HIV replication in vitro, have been described; but most depend on in vitro expansion of CD8(+) T cells, and some show inhibitory activity in HIV-negative individuals.

Protease-activated receptor 2 signaling upregulates angiogenic growth factors in renal cell carcinoma.

Renal cell carcinoma (RCC) is a highly vascular tumor associated with expression of various angiogenic growth factors. The precise process of how these growth factors are regulated in RCC is not fully understood. Recent evidence suggests that protease activated receptors (PARs), a new family of G-protein coupled receptors, play a crucial role in vascular development and tumor progression through a variety of mechanisms.

A novel HIV vaccine adjuvanted by IC31 induces robust and persistent humoral and cellular immunity.

The HIV vaccine strategy that, to date, generated immune protection consisted of a prime-boost regimen using a canarypox vector and an HIV envelope protein with alum, as shown in the RV144 trial. Since the efficacy was weak, and previous HIV vaccine trials designed to generate antibody responses failed, we hypothesized that generation of T cell responses would result in improved protection. Thus, we tested the immunogenicity of a similar envelope-based vaccine using a mouse model, with two modifications: a clade C CN54gp140 HIV envelope protein was adjuvanted by the TLR9 agonist IC31®, and the viral vector was the vaccinia strain NYVAC-CN54 expressing HIV envelope gp120.

Kallikrein-related peptidase-4 initiates tumor-stroma interactions in prostate cancer through protease-activated receptor-1.

In prostate cancer, the mechanism by which the stromal cells surrounding the cancer epithelium become reactive and overproduce growth factors is unclear. Furthermore, the precise process of how these stromal cells stimulate the cancer epithelium is not fully understood. We recently found that protease-activated receptor-1 (PAR-1) in these reactive stromal cells is upregulated.

Prostate-specific kallikreins-2 and -4 enhance the proliferation of DU-145 prostate cancer cells through protease-activated receptors-1 and -2.

A major characteristic of prostate cancer is the elevation of serum levels of prostate-specific antigen (hK3) and hK2, which are tumor markers that correlate with advancing stages of disease. Including hK4, these three kallikrein serine proteases are almost exclusively produced by the prostate. Prostate cancer cells have been recently shown to overexpress protease-activated receptors (PAR), which can be potentially activated by kallikreins and can regulate tumor growth.

Protease-activated receptor-1 upregulates fibroblast growth factor 7 in stroma of benign prostatic hyperplasia.

Background: Benign prostatic hyperplasia (BPH) is characterized by abnormal epithelial and stromal proliferation causing urinary obstruction. Prostate growth is regulated by a variety of growth factors secreted from the stroma, including fibroblast growth factor 7 (FGF-7), a potent epithelial-specific growth factor which is increased in hyperplastic prostate. However, the mediator(s) of FGF-7 over-expression is unclear.

Regulated expression of active biotinylated G-protein coupled receptors in mammalian cells.

We have developed a mammalian expression system suitable for the production of enzymatically biotinylated integral membrane proteins. The key feature of this system is the doxycycline (dox)-regulated co-expression of a secreted variant of Escherichia coli biotin ligase (BirA) and a target protein with a 13-residue biotin acceptor peptide (BioTag) appended to its extracellular domain. Here we describe the expression and functional analysis of three G-protein coupled receptors (GPCRs): protease-activated receptors (PARs) 1 and 2, and the platelet ADP receptor, P2Y(12).

Overexpression of protease-activated receptors-1,-2, and-4 (PAR-1, -2, and -4) in prostate cancer.

Background: Although protease-activated receptors (PARs) have been described to play a role in different malignancies, their expression and biological activity in prostate cancer are mostly unknown.

Methods: PAR expression in radical prostatectomy specimens was investigated by immunohistochemistry (IHC, 40 patients) and RT-PCR. Their role in LNCaP prostate cancer cell migration and Rac1/Cdc42 signaling was assessed with Boyden chamber analysis and Western blot, respectively.

The two upstream open reading frames of oncogene mdm2 have different translational regulatory properties.

Few details are known of the mechanisms through which multiple upstream open reading frames (uORFs) interact to regulate translation in higher eukaryotes. The predominant transcript of oncogene mdm2 in normal human cells (L-mdm2) contains two upstream open reading frames in its 5' leader. Elimination of these two uORFs raises the translational efficiency of the transcript by over 10-fold in HeLa cells.

Protease-activated receptor mediated RhoA signaling and cytoskeletal reorganization in LNCaP cells.

Thrombin and trypsin induce cell signaling through a subclass of G-protein-coupled receptors called the protease-activated receptors (PARs). In many cells, PAR signaling results in the activation of RhoA and other members of the Rho family of small GTPases which are involved in cytoskeletal reorganization. The expression of PARs and their role in the activation of Rho GTPases in prostate cancer cells are not clearly known.

Regulated translation termination at the upstream open reading frame in s-adenosylmethionine decarboxylase mRNA.

The upstream open reading frame (uORF) in the mRNA encoding S-adenosylmethionine decarboxylase is a cis-acting element that confers feedback control by cellular polyamines on translation of this message. Recent studies demonstrated that elevated polyamines inhibit synthesis of the peptide encoded by the uORF by stabilizing a ribosome paused in the vicinity of the termination codon. These studies suggested that polyamines act at the termination step of uORF translation.