Stigma and cervical cancer prevention: A scoping review of the U.S. literature.

Cervical cancer is preventable through HPV vaccination and screening however, uptake falls below national targets. A scoping review was conducted to describe stigmas related to HPV infection and vaccination and cervical cancer and screening in the US. Results were organized into the domains proposed by Stangl and colleagues' Health Stigma and Discrimination Framework. Common drivers of stigma were fear of social judgement and rejection, self-blame, and shame. Positive facilitators included social norms that provided motivation to receive HPV vaccination and screening. Gender and social norms were notable negative facilitators of stigma. HPV infection and cervical cancer resulted in stigma marking through the belief that both result from incautious behavior-either multiple sexual partners or failing to get screening. Stereotyping and prejudice were stigma practices attributed to HPV infection and cervical cancer through these same behaviors. Stigma experiences related to HPV infection, cervical cancer, and abnormal screening results included altered self-image based on perceived/anticipated stigma, as well as discrimination. This review advances understanding of the multiple dimensions of stigma associated with these outcomes in the US population. Three areas warrant additional consideration. Future studies should 1) assess how stigma dimensions affect uptake of cervical cancer preventions efforts; 2) focus on US women most affected by cervical cancer incidence and mortality to identify potential differences in these dimensions and tailor interventions accordingly; 3) include women from geographic areas of the US with high rates of cervical cancer to adapt interventions that address potential regional variations in resources and need.

Qualitative Analysis of Multiple Sources and Dimensions of Stigma Among Older Adults Living With HIV Infection Released From Corrections.

While sources of stigma associated with HIV, incarceration, and aging have been explored separately, the concurrent effects of these multiple sources have been understudied. We conducted in-depth interviews with 48 older adults over 50 years of age with HIV infection who were returning from correctional settings concerning their experiences of stigma. Participants described HIV-related stigma substantially more often than incarceration-related stigma and a greater number of stigma experiences as time passed from release. Anticipated stigma experiences were frequently associated with HIV. Enacted stigma was often related to incarceration. Internalized stigma was associated with both HIV and incarceration. However, participants often described aging as a positive experience of gaining wisdom and control over their life. The findings indicated that multiple sources of stigma affect different dimensions of stigma. Postrelease interventions may benefit from addressing increasing experiences of stigma in the rapidly growing population of older adults living with HIV with a history of incarceration.

Microfluidic device facilitates in vitro modeling of human neonatal necrotizing enterocolitis-on-a-chip.

Necrotizing enterocolitis (NEC) is a deadly gastrointestinal disease of premature infants that is associated with an exaggerated inflammatory response, dysbiosis of the gut microbiome, decreased epithelial cell proliferation, and gut barrier disruption. We describe an in vitro model of the human neonatal small intestinal epithelium (Neonatal-Intestine-on-a-Chip) that mimics key features of intestinal physiology. This model utilizes intestinal enteroids grown from surgically harvested intestinal tissue from premature infants and cocultured with human intestinal microvascular endothelial cells within a microfluidic device. We used our Neonatal-Intestine-on-a-Chip to recapitulate NEC pathophysiology by adding infant-derived microbiota. This model, named NEC-on-a-Chip, simulates the predominant features of NEC, including significant upregulation of proinflammatory cytokines, decreased intestinal epithelial cell markers, reduced epithelial proliferation, and disrupted epithelial barrier integrity. NEC-on-a-Chip provides an improved preclinical model of NEC that facilitates comprehensive analysis of the pathophysiology of NEC using precious clinical samples. This model is an advance toward a personalized medicine approach to test new therapeutics for this devastating disease.

Indole-3-Carbinol-Dependent Aryl Hydrocarbon Receptor Signaling Attenuates the Inflammatory Response in Experimental Necrotizing Enterocolitis.

Necrotizing enterocolitis (NEC) causes significant morbidity and mortality in premature infants; therefore, the identification of therapeutic and preventative strategies against NEC remains a high priority. The ligand-dependent transcription factor aryl hydrocarbon receptor (AhR) is well known to contribute to the regulation of intestinal microbial communities and amelioration of intestinal inflammation. However, the role of AhR signaling in NEC is unclear. Experimental NEC was induced in 4-d-old wild-type mice or mice lacking AhR expression in the intestinal epithelial cells or AhR expression in CD11c+ cells (AhRΔCD11c) by subjecting animals to twice daily hypoxic stress and gavage feeding with formula supplemented with LPS and enteric bacteria. During NEC, compared with wild-type mice treated with vehicle, littermates treated with an AhR proligand, indole-3-carbinol, had reduced expression of Il1b and Marco, a scavenger receptor that mediates dendritic cell activation and the recognition and clearance of bacterial pathogens by macrophages. Furthermore, indole-3-carbinol treatment led to the downregulation of genes involved in cytokine and chemokine, as revealed by pathway enrichment analysis. AhR expression in the intestinal epithelial cells and their cre-negative mouse littermates were similarly susceptible to experimental NEC, whereas AhRΔCD11c mice with NEC exhibited heightened inflammatory responses compared with their cre-negative mouse littermates. In seeking to determine the mechanisms involved in this increased inflammatory response, we identified the Tim-4- monocyte-dependent subset of macrophages as increased in AhRΔCD11c mice compared with their cre-negative littermates. Taken together, these findings demonstrate the potential for AhR ligands as a novel immunotherapeutic approach to the management of this devastating disease.

Interleukin-22 signaling attenuates necrotizing enterocolitis by promoting epithelial cell regeneration.

Necrotizing enterocolitis (NEC) is a deadly intestinal inflammatory disorder that primarily affects premature infants and lacks adequate therapeutics. Interleukin (IL)-22 plays a critical role in gut barrier maintenance, promoting epithelial regeneration, and controlling intestinal inflammation in adult animal models. However, the importance of IL-22 signaling in neonates during NEC remains unknown. We investigated the role of IL-22 in the neonatal intestine under homeostatic and inflammatory conditions by using a mouse model of NEC. Our data reveal that Il22 expression in neonatal murine intestine is negligible until weaning, and both human and murine neonates lack IL-22 production during NEC. Mice deficient in IL-22 or lacking the IL-22 receptor in the intestine display a similar susceptibility to NEC, consistent with the lack of endogenous IL-22 during development. Strikingly, treatment with recombinant IL-22 during NEC substantially reduces inflammation and enhances epithelial regeneration. These findings may provide a new therapeutic strategy to attenuate NEC.

Breast Milk Enhances Growth of Enteroids: An Ex Vivo Model of Cell Proliferation.

Human small intestinal enteroids are derived from the crypts and when grown in a stem cell niche contain all of the epithelial cell types. The ability to establish human enteroid ex vivo culture systems are important to model intestinal pathophysiology and to study the particular cellular responses involved. In recent years, enteroids from mice and humans are being cultured, passaged, and banked away for future use in several laboratories across the world. This enteroid platform can be used to test the effects of various treatments and drugs and what effects are exerted on different cell types in the intestine. Here, a protocol for establishing primary stem cell-derived small intestinal enteroids derived from neonatal mice and premature human intestine is provided. Moreover, this enteroid culture system was utilized to test the effects of species-specific breast milk. Mouse breast milk can be obtained efficiently using a modified human breast pump and expressed mouse milk can then be used for further research experiments. We now demonstrate the effects of expressed mouse, human, and donor breast milk on the growth and proliferation of enteroids derived from neonatal mice or premature human small intestine.