Nanoparticle-Encapsulated Bryostatin-1 Activates α-Secretase and PKC Isoforms In vitro and Facilitates Acquisition and Retention of Spatial Learning in an Alzheimer's Disease Mouse Model.

BACKGROUND: Alzheimer's disease (AD) animal models have revealed neuroprotective actions of Bryostatin-1 mediated by activation of novel PKC isoforms, suppression of beta-amyloid and downregulation of inflammatory and angiogenic events, making Bryostatin-1 an attractive candidate for attenuating AD-associated neural, vascular, and cognitive disturbances. OBJECTIVE: To further enhance Bryostatin-1 efficacy, nanoparticle-encapsulated Bryostatin-1 formulations were prepared. METHODS: We compared nano-encapsulated and unmodified Bryostatin-1 in in vitro models of neuronal PKC-d, PKC-e isoforms, α-secretase and studied nano-encapsulated Bryostatin-1 in an AD mouse model of spatial memory (BC3-Tg (APPswe, PSEN1 dE9) 85Dbo/J mice). RESULTS: We found that nanoencapsulated Bryostatin-1 formulations displayed activity greater or equal to that of unmodified Bryostatin-1 in PKC-δ and -ε and α-secretase activation assays. We next evaluated how treatment with a nanoencapsulated Bryostatin-1 formulation facilitated spatial learning in the Morris water maze. AD transgenic mice (6.5 to 8 months of age) were treated with nanoparticle encapsulated Bryostatin-1 formulation (1, 2.5, or 5 µg/mouse) three times the week before testing and then daily for each of the 5 days of testing. Across the acquisition phase, mice treated with nanoencapsulated Bryostatin-1 had shorter latencies, increased % time in the target zone and decreased % time in the opposite quadrant. The mice were given retention testing after a 2-week period without drug treatment. Mice treated with nanoencapsulated Bryostatin-1 had shorter latencies to find the escape platform, indicating retention of spatial memory. CONCLUSION: These data suggest that cognitive deficits associated with AD could be treated using highly potent nanoparticle-encapsulated formulations of Bryostatin-1.

An international comparative public health analysis of sex trafficking of women and girls in eight cities: achieving a more effective health sector response.

Sex trafficking, trafficking for the purpose of forced sexual exploitation, is a widespread form of human trafficking that occurs in all regions of the world, affects mostly women and girls, and has far-reaching health implications. Studies suggest that up to 50 % of sex trafficking victims in the USA seek medical attention while in their trafficking situation, yet it is unclear how the healthcare system responds to the needs of victims of sex trafficking. To understand the intersection of sex trafficking and public health, we performed in-depth qualitative interviews among 277 antitrafficking stakeholders across eight metropolitan areas in five countries to examine the local context of sex trafficking. We sought to gain a new perspective on this form of gender-based violence from those who have a unique vantage point and intimate knowledge of push-and-pull factors, victim health needs, current available resources and practices in the health system, and barriers to care. Through comparative analysis across these contexts, we found that multiple sociocultural and economic factors facilitate sex trafficking, including child sexual abuse, the objectification of women and girls, and lack of income. Although there are numerous physical and psychological health problems associated with sex trafficking, health services for victims are patchy and poorly coordinated, particularly in the realm of mental health. Various factors function as barriers to a greater health response, including low awareness of sex trafficking and attitudinal biases among health workers. A more comprehensive and coordinated health system response to sex trafficking may help alleviate its devastating effects on vulnerable women and girls. There are numerous opportunities for local health systems to engage in antitrafficking efforts while partnering across sectors with relevant stakeholders.

Sex trafficking and health care in Metro Manila: identifying social determinants to inform an effective health system response.

This social science case study examines the sex trafficking of women and girls in Metro Manila through a public health lens. Through key informant interviews with 51 health care and anti-trafficking stakeholders in Metro Manila, this study reports on observations about sex trafficking in Metro Manila that provide insight into understanding of risk factors for sex trafficking at multiple levels of the social environment: individual (for example, childhood abuse), socio-cultural (for example, gender inequality and a "culture of migration"), and macro (for example, profound poverty caused, inter alia, by environmental degradation disrupting traditional forms of labor). It describes how local health systems currently assist sex-trafficking victims, and provides a series of recommendations, ranging from prevention to policy, for how health care might play a larger role in promoting the health and human rights of this vulnerable population.

Identification of HIV-infected 12- to 24-year-old men and women in 15 US cities through venue-based testing.

OBJECTIVE: To test whether "venue-based testing" could identify human immunodeficiency virus (HIV) infection in US youth, 12 to 24 years of age, who were otherwise not aware of their infection. Racial and ethnic minority women and men who have sex with men (WSM and MSM) compose the majority of new HIV cases among adolescents and young adults. DESIGN: Cross-sectional study. SETTING: Selected venues in communities surrounding the 15 Adolescent Trials Network for HIV/AIDS Interventions (ATN) clinical sites over a 3-month period. PARTICIPANTS: At each venue, ATN sites recruited 20 to 30 English- or Spanish-speaking at-risk youth (12 to 24 years of age), resulting in a total of 1217 study participants, including 611 MSM and 606 WSM. Intervention Venue-based HIV testing with 2 components: an anonymous audio computer-assisted self-administered interview and an anonymous HIV antibody assay. MAIN OUTCOME MEASURE: The prevalence of HIV infection in MSM and WSM. RESULTS: The prevalence of HIV infection in MSM and WSM was 15.3% and 0.3%, respectively. Sixty percent of the MSM and 100% of the WSM claimed to not know of their infection. CONCLUSION: Venue-based testing may be an important strategy to identify HIV-infected younger MSM; however, other strategies are needed for WSM.

The role of community resource assessments in the development of 15 adolescent health community-researcher partnerships.

BACKGROUND: Connect to Protect (C2P): Partnerships for Youth Prevention Interventions is an initiative that alters the community's structural elements to reduce youth HIV rates. OBJECTIVES: This study details a community resource assessment and describes how resources were evaluated in the context of local needs. METHODS: Fifteen sites developed a community resource list, conducted a brief survey, created a youth service directory, and mapped where disease prevalence and community resources intersected. Sites also completed a survey to review and verify local site findings. RESULTS: On average, sites identified 267 potential community resources. Sites narrowed their resource list to conduct a brief survey with 1,162 agencies; the site average was 78. Final products of this process included maps comparing resources with risk data. CONCLUSIONS: The evaluation of local resources is an important initial step in partnership development and is essential for the success of health promotion and disease prevention interventions that target adolescents.

Partnership selection and formation: a case study of developing adolescent health community-researcher partnerships in fifteen U.S. communities.

PURPOSE: This study describes the partner selection process in 15 U.S. communities developing community-researcher partnerships for the Connect to Protect (C2P): Partnerships for Youth Prevention Interventions, an initiative of the Adolescent Trials Network for human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) Interventions. METHODS: Each site generated an epidemiological profile of urban youth in their community, selected a focus population and geographic area of youth at risk for HIV, conducted a series of successive structured interviews, and engaged in a process of relationship-building efforts culminating in a collaborative network of community agencies. RESULTS: Sites chose as their primary target population young women who have sex with men (n = 8 sites), young men who have sex with men (n = 6), and intravenous drug users (n = 1). Of 1162 agencies initially interviewed, 281 of 335 approached (84%) agreed to join the partnership (average 19/site). A diverse array of community agencies were represented in the final collaborative network; specific characteristics included: 93% served the sites' target population, 54% were predominantly youth oriented, 59% were located in the geographical area of focus, and 39% reported provision of HIV/STI (sexually transmitted infection) prevention services. Relationship-building activities, development of collaborative relationships, and lessons learned, including barriers and facilitators to partnership, are also described. CONCLUSIONS: Study findings address a major gap in the community partner research literature. Health researchers and policymakers need an effective partner selection framework whereby community-researcher partnerships can develop a solid foundation to address public health concerns.