The common parasite Toxoplasma gondii induces prostatic inflammation and microglandular hyperplasia in a mouse model

BACKGROUND: Inflammation is the most prevalent and widespread histological finding in the human prostate, and associates with the development and progression of benign prostatic hyperplasia and prostate cancer. Several factors have been hypothesized to cause inflammation, yet the role each may play in the etiology of prostatic inflammation remains unclear. This study examined the possibility that the common protozoan parasite Toxoplasma gondii induces prostatic inflammation and reactive hyperplasia in a mouse model. METHODS: Male mice were infected systemically with T. gondii parasites and prostatic inflammation was scored based on severity and focality of infiltrating leukocytes and epithelial hyperplasia. We characterized inflammatory cells with flow cytometry and the resulting epithelial proliferation with bromodeoxyuridine (BrdU) incorporation. RESULTS: We found that T. gondii infects the mouse prostate within the first 14 days of infection and can establish parasite cysts that persist for at least 60 days. T. gondii infection induces a substantial and chronic inflammatory reaction in the mouse prostate characterized by monocytic and lymphocytic inflammatory infiltrate. T. gondii-induced inflammation results in reactive hyperplasia, involving basal and luminal epithelial proliferation, and the exhibition of proliferative inflammatory microglandular hyperplasia in inflamed mouse prostates. CONCLUSIONS: This study identifies the common parasite T. gondii as a new trigger of prostatic inflammation, which we used to develop a novel mouse model of prostatic inflammation. This is the first report that T. gondii chronically encysts and induces chronic inflammation within the prostate of any species. Furthermore, T. gondii-induced prostatic inflammation persists and progresses without genetic manipulation in mice, offering a powerful new mouse model for the study of chronic prostatic inflammation and microglandular hyperplasia

Cellular basis of urothelial squamous metaplasia: roles of lineage heterogeneity and cell replacement

Although the epithelial lining of much of the mammalian urinary tract is known simply as the urothelium, this epithelium can be divided into at least three lineages of renal pelvis/ureter, bladder/trigone, and proximal urethra based on their embryonic origin, uroplakin content, keratin expression pattern, in vitro growth potential, and propensity to keratinize during vitamin A deficiency. Moreover, these cells remain phenotypically distinct even after they have been serially passaged under identical culture conditions, thus ruling out local mesenchymal influence as the sole cause of their in vivo differences. During vitamin A deficiency, mouse urothelium form multiple keratinized foci in proximal urethra probably originating from scattered K14-positive basal cells, and the keratinized epithelium expands horizontally to replace the surrounding normal urothelium. These data suggest that the urothelium consists of multiple cell lineages, that trigone urothelium is closely related to the urothelium covering the rest of the bladder, and that lineage heterogeneity coupled with cell migration/replacement form the cellular basis for urothelial squamous metaplasia

Differences in the carcinogenic evaluation of glyphosate between the International Agency for Research on Cancer (IARC) and the European Food Safety Authority (EFSA)

The International Agency for Research on Cancer (IARC) Monographs Programme identifies chemicals, drugs, mixtures, occupational exposures, lifestyles and personal habits, and physical and biological agents that cause cancer in humans and has evaluated about 1000 agents since 1971. Monographs are written by ad hoc Working Groups (WGs) of international scientific experts over a period of about 12 months ending in an eight-day meeting. The WG evaluates all of the publicly available scientific information on each substance and, through a transparent and rigorous process,1 decides on the degree to which the scientific evidence supports that substance's potential to cause or not cause cancer in humans. For Monograph 112,2 17 expert scientists evaluated the carcinogenic hazard for four insecticides and the herbicide glyphosate.3 The WG concluded that the data for glyphosate meet the criteria for classification as a probable human carcinogen. The European Food Safety Authority (EFSA) is the primary agency of the European Union for risk assessments regarding food safety. In October 2015, EFSA reported4 on their evaluation of the Renewal Assessment Report5 (RAR) for glyphosate that was prepared by the Rapporteur Member State, the German Federal Institute for Risk Assessment (BfR). EFSA concluded that ?glyphosate is unlikely to pose a carcinogenic hazard to humans and the evidence does not support classification with regard to its carcinogenic potential?. Addendum 1 (the BfR Addendum) of the RAR5 discusses the scientific rationale for differing from the IARC WG conclusion. Serious flaws in the scientific evaluation in the RAR incorrectly characterise the potential for a carcinogenic hazard from exposure to glyphosate. Since the RAR is the basis for the European Food Safety Agency (EFSA) conclusion,4 it is critical that these shortcomings are corrected

Developing a global medicine student pre- and post-travel curriculum

Abstract Background The popularity of short-term global health experiences amongst US medical students has been increasing. However, it remains a challenge for medical schools to comprehensively prepare students to work in an international environment and to contribute in ethically responsible and meaningful ways. Students of the Global Medicine program (GMED) of the UIC College of Medicine Center for Global Health set out to develop a pre-and-post travel curriculum that addresses some of these challenges. Methods The students surveyed the literature of 66 published global health curricula and identified aspects of pre-and-post travel training that were found to be under-addressed. They then developed a curriculum in conjunction with GMED faculty that incorporated these identified aspects of pre-and-post travel training. Results Five aspects of pre-and-post travel training were identified as being under-addressed in the literature while traveling. These domains include: [1] examining power relations associated with neo-colonization between and within countries; [2] training for bi-directional learning; [3] examining motivations and goals for participating in global health; [4] addressing personal resiliency and psychosocial wellbeing related to students’ travel, and; [5] reflecting on the challenging aspects of the fieldwork experience. Conclusions The student-driven curriculum is being integrated into the GMED program through structured didactic sessions, one-on-one mentor meetings and small group discussions. Once students have traveled, the curriculum will be evaluated with the foreign partners they visited

Potential New Approaches for Prostate Cancer Management in Resource-Limited Countries in Africa

Prostate cancer is a major male malignancy in many sub-Saharan countries in Africa. Because of resource limitations, screening, early detection, diagnosis, and curative treatments are not available for many men on the subcontinent, and there are even barriers to the treatment of advanced-stage metastatic prostate cancer. We are making the case for new approaches to the detection, diagnosis, and treatment of this malignancy in sub-Saharan Africa and other low-resource regions—approaches that differ from the ones available and used in high-income countries. The development of one-step dipstick-type detection assays of serum prostate-specific antigen (PSA) offers an approach to prostate cancer detection, treatment and monitoring that circumvents issues related to laboratory quality control and is also low-cost. Curative-intent treatments of early-stage prostate cancer are often unavailable in low-resource contexts, and most prostate cancers are not detected in Africa until they are at an advanced stage. Hence, androgen deprivation treatments, including orchiectomy and older low-cost drugs, offer feasible and affordable approaches to prolong survival and sustain a reasonable quality of life. However, clinical trials are needed to identify which of these androgen deprivation treatments are most efficacious and best tolerated to make progress in providing medical care for men with prostate cancer in sub-Saharan Africa and other low- and lower-middle-income areas around the world