University of Richmond

Primary sclerosing cholangitis-associated UC (PSC-UC) carries excess colorectal neoplasia despite often mild-appearing endoscopy, implicating persistent microscopic inflammation and microbiota-bile acid (BA) dysfunction. To test whether PSC-UC neoplasia is driven by transferable microbiota-mediated inflammation linked to secondary BA loss. Surveillance colonoscopies (2012-2022) from PSC-UC (n=251) and UC-only (n=8839) were compared for segmental endoscopic/histological activity and dysplasia. We generated multidrug resistance protein 2 (MDR2)-/- × interleukin (IL)-10-/- double-knockout (DKO) mice and used germ-free (GF) derivation, faecal microbiota transplantation (FMT), antibiotic conditioning and cohousing with shotgun metagenomics and liquid chromatography-tandem mass spectrometry BA profiling. PSC-UC showed greater inflammatory activity and a right-shifted dysplasia burden versus UC-only. Under specific-pathogen-free conditions, DKO mice developed early right-predominant colitis and multifocal dysplasia progressing with age. DKO communities were depleted of 7α-dehydroxylation capacity with near absence of deoxycholic and lithocholic acids and no enrichment of canonical bacterial genotoxins. GF DKO mice were protected, whereas live DKO donor FMT reinstated severe colitis and dysplasia; sterile-filtered stool supernatant was inactive. IL-10-/- donor FMT or cohousing attenuated colitis and increased recipient secondary BA, whereas wild-type/MDR2-/- donor transfers were non-colitogenic. In GF DKO mice, direct deoxycholic acid repletion caused hepatotoxicity. PSC-UC neoplasia associates with transmissible microbiota-dependent inflammation and secondary BA deficiency. Controlled restoration of BA-transforming microbial functions, rather than indiscriminate secondary BA replacement, is a rational translational direction.

BackgroundUsing English-only assessment tools with Spanish-speaking patients can lead to miscommunication and inadequate care. The current study translates the commonly used Clinical Opiate Withdrawal Scale (COWS) into La Escala Clínica de Síndrome Abstinencia de Opiáceos (ECAO) for use by healthcare workers to use with Spanish-speaking patients.MethodsFirst, the COWS was translated using standard forward/backward methods. Next attitudes and feedback about the ECAO were assessed via a mixed-methods pilot study.ResultsThe translation went according to plan. The final sample size of the pilot study was N=107 healthcare providers (Mage = 40.00 years; woman = 58.88%; master’s degree = 42.06%). The translation was rated as accurate (M=7.83; SD = 1.71; range 4–10) with a majority (62.62%) of participants rating it at an 8 or above. Ratings of acceptability, appropriateness, feasibility, understandability, and actionability were also quite high, with agreement across questions in these sections ranging from 72.09–95.33%. Qualitative results highlighted favorability toward the ECAO such as its accurate and culturally sensitive translation with areas of improvement including use of overly medical terms.ConclusionBased on the results of this pilot study, the ECAO appears to be an accurate, feasible, useful tool for Spanish-speaking healthcare workers who treat patients struggling with opioid withdrawal. The free availability of the Spanish-language ECAO will help patients and providers communicate adequately in order to determine the extent of opioid withdrawal accuracy as well as develop appropriate treatment plans.

This paper proposes violent capital as an analytic tool to explore violence and its relation to the social order. Following Pierre Bourdieu on cultural capital, I suggest we think of violence as a potential asset that can be invested in or exchanged for another asset, position, or status. After an introductory discussion of conceptualization and operationalization, and to bring the concept to life and suggest analytic utility, the paper turns to violent capital and hierarchies. Given the centrality of states to the history of violence (Tilly 1992; Mann 1986, 1993; North, Wallis, and Weingast 2009), examining violent capital and hierarchies provides further insights into the nature of states and state-building, and vice versa. The paper uses historical cases to show three different ways of the relation of violent capital to status, that also expand our understanding of the rise of the state: antiquity (Sparta and Rome), medieval Europe (knights), and modern armies. These cases reveal variation in how violent capital is invested and exchanged and in its value for hierarchies. These cases also suggest additional dimensions to the historical evolution of the modern state and “coercion” as more than resources for physical force: this evolution is also disciplining, compartmentalizing, and subordinating violent capital. The paper concludes with a research agenda and further potential analytic utility.

Abstract Background There is growing evidence that ablation of high-grade anal dysplasia prevents the development of anal cancer. Despite this, anal cancer screening uptake is lagging in many clinical settings. We conducted a national survey study for HIV providers to assess beliefs about anal cancer screening, barriers to screening and needs for implementing a screening program in their clinic. Methods An 18-question survey was built on REDCap and distributed among medical providers that care for adults with HIV in the United States. The online survey was distributed through an HIV society listserv, social media platforms and direct messaging of academic infectious disease program directors. Results Two hundred and sixty-eight participants completed a survey, which resulted in a 2.8% response rate. Of those, 227 participants were included in further analysis. Sixty two percent (n=141) were women, 63% were attendings (n=144) and 60% were infectious disease specialists (n=136). Forty participants did not offer anal cancer screening (18%). Of the 187 participants that offered screening, 81% (n=152) performed their own anal pap smears and 72% (n=120) referred out for anal biopsies. Of those that offered anal cancer screening, the most common challenge was lack of interest from patients (30%, n=57). Among those that did not offer anal cancer screening, 98% (n=39) stated they were motivated or fairly motivated to offer screening if they had an established pathway. And 75% (n=30) wanted to receive training for anal Pap smears. The most common barrier to screening in this group was lack of referral options (53%, n=21) and the most pressing need in order to start a screening program was establishing referral pathways (53%, n=21). Conclusion There are several barriers that need to be addressed in order to empower HIV providers to screen for anal cancer. For those without an established anal cancer screening program, the vast majority would be motivated to screen their patients if they have a screening program in place. The most pressing needs for this group are establishing referral pathways to specialists and increasing training opportunities for themselves or staff. Disclosures All Authors: No reported disclosures