Xenotransplanted human organoids identify transepithelial zinc transport as a key mediator of intestinal adaptation.

Short bowel syndrome (SBS) leads to severe morbidity and mortality. Intestinal adaptation is crucial in improving outcomes. To understand the human gene pathways associated with adaptation, we perform single-cell transcriptomic analysis of human small intestinal organoids explanted from mice with experimental SBS. We show that transmembrane ion pathways, specifically the transepithelial zinc transport pathway genes SLC39A4 and SLC39A5, are upregulated in SBS. This discovery is corroborated by an external dataset, bulk RT-qPCR, and Western blots. Oral zinc supplementation is shown to improve survival and weight gain of SBS mice and increase the proliferation of intestinal crypt cells in vitro. Finally, we identify the upregulation of SLC39A5 and associated transcription factor KLF5 in biopsied intestinal tissue specimens from patients with SBS. Thus, we identify zinc supplementation as a potential therapy for SBS and describe a xenotransplantation model that provides a platform for discovery in other intestinal diseases.

Reluctant Saviors: Professional ambivalence, cultural imaginaries, and deservingness construction in naloxone provision.

Professions compete over jurisdictions by laying claim to specific tasks. Research shows that they enhance their professional status by siphoning off tasks and seizing control of social problems that belong to other professions. Not all tasks are equally desirable, though. Studies find that workers resist helping stigmatized groups or taking on "unsolvable" social problems. This raises a critical question for social scientists: How do professionals respond when opportunities for jurisdictional expansion are contingent on aiding a stigmatized population? Our study draws on research from the sociology of culture, professions, and stigma and empirical evidence about naloxone provision to develop a theory of professional ambivalence that explains how professionals respond to this fundamental tension. In response to rising rates of overdose deaths in the U.S., many cities have adopted naloxone provision programs in which first responders-police, firefighters, and EMTs-carry and administer naloxone, an opioid overdose antidote. For police and firefighters, this task enables them to venture into medical territory, but for all three professionals, it requires working with the stigmatized population of people who use drugs. We use abductive analysis of qualitative interviews (n = 20) conducted in a Midwestern metropolitan area from 2018 to 2019 to explore professionals' attitudes about naloxone. We find that professionals' willingness to take on new tasks is largely grounded in how they construct patients as deserving or undeserving of care. Deservingness construction is a constitutive process through which first responders draw on cultural imaginaries about addiction and treatment as well as their own experiences providing naloxone. This results in three mechanisms of deservingness construction-experiential, behavioral, and interactional-that reinforce cultural imaginaries and affect how they think about patients, naloxone, and addiction. Findings contribute to theory of professional ambivalence and offer policy implications to enhance the effectiveness of naloxone provision programs.

Head and Neck Cystic Lesions: A Cytology Review of Common and Uncommon Entities.

BACKGROUND: Cystic lesions of the head and neck are a diagnostic challenge since they are seen in the clinical presentation of a wide variety of conditions. Herein, common and uncommon entities that present as cystic lesions in the head and neck are reviewed. SUMMARY: In this study, peer-reviewed articles were selected using the database PubMed, Google, Google Scholar, and Scopus. Emphasis was placed on peer-reviewed articles that discuss the cytomorphology and differential diagnosis of entities that present as cystic lesions of the head and neck. In the anterior neck, both benign and malignant neoplasms can present, including papillary thyroid carcinoma (PTC), thyroid adenomatoid nodule, parathyroid cysts, and thyroglossal cysts. In the lateral neck, branchial cleft cyst, PTC, ectopic thyroid cyst, and squamous cell carcinomas (human papilloma virus and non- human papilloma virus-related) are common. Age over 40 years raises the possibility of malignancy. In the deep neck, mostly benign cystic entities occur such as a pleomorphic adenoma, paraganglioma, schwannoma, branchial cyst, epidermal inclusion cyst, and lymphoepithelial cyst. Lesions with squamous cell features can pose diagnostic dilemmas. CONCLUSION: Cytologic examination of head and neck cysts can provide valuable information regarding the nature of the cystic lesions. Information about anatomic site and clinical history can assist with the differential diagnoses. Ancillary studies can improve the diagnosis in some cases. Each case should be evaluated very carefully since there are a wide variety of congenital conditions, infectious/inflammatory conditions, benign neoplasms, and primary and secondary malignancies presenting as a cystic mass in the head and neck.