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1.
J Immunol Methods ; 525: 113599, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38081407

RESUMO

Intestinal transplantation is the definitive treatment for intestinal failure. However, tissue rejection and graft-versus-host disease are relatively common complications, necessitating aggressive immunosuppression that can itself pose further complications. Tracking intraluminal markers in ileal effluent from standard ileostomies may present a noninvasive and sensitive way to detect developing pathology within the intestinal graft. This would be an improvement compared to current assessments, which are limited by poor sensitivity and specificity, contributing to under or over-immunosuppression, respectively, and by the need for invasive biopsies. Herein, we report an approach to reproducibly analyze ileal fluid obtained through stoma sampling for antimicrobial peptide/protein concentrations, reasoning that these molecules may provide an assessment of intestinal homeostasis and levels of intestinal inflammation over time. Concentrations of lysozyme (LYZ), myeloperoxidase (MPO), calprotectin (S100A8/A9) and ß-defensin 2 (DEFB2) were assessed using adaptations of commercially available enzyme-linked immunosorbent assays (ELISAs). The concentration of α-defensin 5 (DEFA5) was assessed using a newly developed sandwich ELISA. Our data support that with proper preparation of ileal effluent specimens, precise and replicable determination of antimicrobial peptide/protein concentrations can be achieved for each of these target molecules via ELISA. This approach may prove to be reliable as a clinically useful assessment of intestinal homeostasis over time for patients with ileostomies.


Assuntos
Peptídeos Antimicrobianos , alfa-Defensinas , Humanos , Intestinos , Ensaio de Imunoadsorção Enzimática , Biópsia
2.
Med Sci Educ ; 32(3): 733-745, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35493984

RESUMO

Purpose: The COVID-19 pandemic has demonstrated the importance for medical professionals to engage in work transcending national borders and to deeply understand perspectives of health in other countries. Internationalization of medical education can play a key role to that end, by preparing culturally competent and globally conscious medical healthcare professionals.The aim of this scoping review is to identify current practices and formats in internationalization in medical education, which to date has received sparse academic attention. The need for this review is heightened amid COVID-19 where a clearer understanding of current internationalization efforts can inform more effective practice. We also explore if the motivations driving internationalization activities in medicine align with current practice and formats based on a framework of thematic categories found in the field of international higher education. In addition, we identify gaps in existing research. Methods: Using a scoping review, an international and interdisciplinary research team employed a comprehensive search strategy to identify publications on existing efforts in IoME, published from January 1, 2000, to December 31, 2020, in Scopus, PubMed/Medline, Google Scholar, and Web of Science. Inclusion/exclusion criteria were applied to identify relevant data from publication titles, abstracts, and main texts, which were subsequently summarized. Coding schemes were developed based on models for comprehensive internationalization in higher education. Results: 350 articles met the inclusion criteria. Most articles originated from the high-income countries of the Global North and accounted for a literature base favoring perspectives and understandings that were typically representative of this region. Whereas motivations for internationalizing medical curricula in high-income countries were generally rooted in a model of social transformation/justice/health equity, drivers relating to competition and workforce preparation were common in the low- and middle-income countries.Importantly, the motivations driving internationalization activities generally did not align well with reported internationalization formats, which included student mobility, international curricula at home, and global partnerships. There was a disconnect between what medical curricula/professionals hope to accomplish and the reality of practice on the ground. Discussion and Conclusion: There is a need for a common definition of internationalization of medical education and a more balanced and unbiased literature base, capturing the full spectrum of internationalization activities existing in both the Global North and South. International partnership frameworks need to equally benefit institutions of both the Global North and Global South. Currently, institutions in the low- and middle-income countries generally cater to the needs and interests of their high-income counterparts. There are concerns about student mobility from high-income countries to low- and middle-income countries. Finally, medical education should be more inclusive and all medical students should gain access to international perspectives and experiences. Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-022-01553-6.

3.
Curr Opin Organ Transplant ; 27(2): 119-125, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35232925

RESUMO

PURPOSE OF REVIEW: The intestine is the most immunologically complex solid organ allograft with the greatest risk of both rejection and graft-versus-host disease (GVHD). High levels of immunosuppression are required, further increasing morbidity. Due to low volume of transplants and few centers with experience, there is paucity of evidence-based, standardized, and effective therapeutic regimens. We herein review the most recent data about immunosuppression, focusing on novel and emerging therapies. RECENT FINDINGS: Recent data are moving the field toward increasing use of basilixumab and consideration of alemtuzumab for induction and inclusion of mammalian target of rapamycin inhibitors and antimetabolites for maintenance. For rejection, we highlight novel roles for tumor necrosis factor-α inhibition, α4ß7 integrin inhibition, microbiome modulation, desensitization protocols, and tolerance induction strategies. We also highlight emerging novel therapies for GVHD, especially the promising role of Janus kinase inhibition. SUMMARY: New insights into immune pathways associated with rejection and GVHD in intestinal allografts have led to an evolution of therapies from broad-based immunosuppression to more targeted strategies that hold promise for reducing morbidity from infection, rejection, and GVHD. These should be the focus of further study to facilitate their widespread use.


Assuntos
Doença Enxerto-Hospedeiro , Rejeição de Enxerto/prevenção & controle , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Terapia de Imunossupressão , Imunossupressores/efeitos adversos , Intestinos/transplante , Transplante Homólogo
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