Nutrient scavenging-fueled growth in pancreatic cancer depends on caveolae-mediated endocytosis under nutrient-deprived conditions.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by its nutrient-scavenging ability, crucial for tumor progression. Here, we investigated the roles of caveolae-mediated endocytosis (CME) in PDAC progression. Analysis of patient data across diverse datasets revealed a strong association of high caveolin-1 (Cav-1) expression with higher histologic grade, the most aggressive PDAC molecular subtypes, and worse clinical outcomes. Cav-1 loss markedly promoted longer overall and tumor-free survival in a genetically engineered mouse model. Cav-1-deficient tumor cell lines exhibited significantly reduced proliferation, particularly under low nutrient conditions. Supplementing cells with albumin rescued the growth of Cav-1-proficient PDAC cells, but not in Cav-1-deficient PDAC cells under low glutamine conditions. In addition, Cav-1 depletion led to significant metabolic defects, including decreased glycolytic and mitochondrial metabolism, and downstream protein translation signaling pathways. These findings highlight the crucial role of Cav-1 and CME in fueling pancreatic tumorigenesis, sustaining tumor growth, and promoting survival through nutrient scavenging.

Adherence to PrEP Among Young Men Who Have Sex With Men Participating in a Sexual Health Services Demonstration Project in Alameda County, California.

BACKGROUND: Young men of color who have sex with men face a continual increase in rates of HIV infection. Pre-exposure prophylaxis (PrEP) is an important prevention method for these young men. SETTING: The Connecting Resources for Urban Sexual Health (CRUSH) demonstration project provided sexual health services, including PrEP, to young men who have sex with men aged 18-29 years. We report on adherence and factors influencing it. METHODS: Participants were offered HIV and sexually transmitted infection testing, prevention counseling, PrEP, and when appropriate, sexually transmitted infection treatment and postexposure prophylaxis. Participants taking PrEP had erythrocyte tenofovir diphosphate and emtricitabine levels measured through dried blood spot testing at 4, 12, and 24 weeks to estimate medication adherence. Participants also completed surveys to assess demographic and psychosocial measures. RESULTS: From February 2014 to November 2015, CRUSH enrolled 257 participants. Ninety-three percent started PrEP, 81% of whom initiated it at their first visit. Twelve percent required postexposure prophylaxis before starting PrEP. Adherence at protective levels was initially high with 87% demonstrating levels consistent with at least 4 doses per week at week 4, compared with 77% at the 48-week follow-up. African American race, exposure to violence, and having survival needs were associated with significantly lower levels of adherence [odds ratio (OR): 0.33; confidence interval (CI): 0.11 to 0.97, P < 0.04; OR: 0.79; CI: 0.59 to 1.04, P < 0.10; OR: 0.51; CI: 0.24 to 1.05, P < 0.07]. CONCLUSIONS: Most young men who initiate PrEP adhere at levels that confer protection against HIV infection. Interventions should account for differences in life experiences, particularly addressing the structural challenges facing young African American men.

The Effect of Patient Navigation on the Likelihood of Engagement in Clinical Care for HIV-Infected Individuals Leaving Jail.

OBJECTIVES: To compare the effectiveness of patient navigation-enhanced case management in supporting engagement in HIV care upon release from jail relative to existing services. METHODS: We randomized 270 HIV-infected individuals to receive navigation-enhanced case management for 12 months or standard case management for 90 days following release from jail between 2010 and 2013. Participants were interviewed at 2, 6, and 12 months after release. We abstracted medical data from jail and city health records. RESULTS: Patient navigation-enhanced case management resulted in greater linkage to care within 30 days of release (odds ratio [OR] = 2.15; 95% confidence interval [CI] = 1.23, 3.75) and consistent retention over 12 months (OR = 1.95; 95% CI = 1.11, 3.46). Receipt of treatment for substance use disorders in jail also resulted in early linkage (OR = 4.06; 95% CI = 1.93, 8.53) and retention (OR = 2.52; 95% CI = 1.21, 5.23). Latinos were less likely to be linked to (OR = 0.35; 95% CI = 0.14, 0.91) or retained in (OR = 0.28; 95% CI = 0.09, 0.82) HIV care. CONCLUSIONS: Patient navigation supports maintaining engagement in care and can mitigate health disparities, and should become the standard of care for HIV-infected individuals leaving jail.

Patient navigation facilitates medical and social services engagement among HIV-infected individuals leaving jail and returning to the community.

HIV-infected individuals leaving jails, facilities typically used to confine accused persons awaiting trial or to incarcerate persons for minor offenses, often face barriers to engagement with medical and social-support services. Patient navigation is a model that may ease these barriers by supporting individuals in negotiating fragmented and highly bureaucratic systems for services and care. While there is evidence linking navigation to a reduction in health disparities, little is known about the mechanisms by which the model works. We present findings of an ethnographic study of interactions between navigators and their clients: HIV-infected men and women recently released from jails in San Francisco, California. We conducted 29 field observations of navigators as they accompanied their clients to appointments, and 40 in-depth interviews with clients and navigators. Navigators worked on strengthening clients' abilities to engage with social-services and care systems. Building this strength required navigators to gain clients' trust by leveraging their own similar life experiences or expressing social concordance. After establishing meaningful connections, navigators spent time with clients in their day-to-day environments serving as mentors while escorting clients to and through their appointments. Intensive time spent together, in combination with a shared background of incarceration, HIV, and drug use, was a critical mechanism of this model. This study illustrates that socially concordant navigators are well positioned to facilitate successful transition to care and social-services engagement among a vulnerable population.