Immunological mechanisms of fecal microbiota transplantation in recurrent Clostridioides difficile infection

Fecal microbiota transplantation (FMT) is a successful method for treating recurrent Clostridioides difficile (C. difficile) infection (rCDI) with around 90% efficacy. Due to the relative simplicity of this approach, it is being widely used and currently, thousands of patients have been treated with FMT worldwide. Nonetheless, the mechanisms underlying its effects are just beginning to be understood. Data indicate that FMT effectiveness is due to a combination of microbiological direct mechanisms against C. difficile, but also through indirect mechanisms including the production of microbiota-derived metabolites as secondary bile acids and short chain fatty acids. Moreover, the modulation of the strong inflammatory response triggered by C. difficile after FMT seems to rely on a pivotal role of regulatory T cells, which would be responsible for the reduction of several cells and soluble inflammatory mediators, ensuing normalization of the intestinal mucosal immune system. In this minireview, we analyze recent advances in these immunological aspects associated with the efficacy of FMT.     

Validity of the Central Sensitization Inventory (CSI) through Rasch analysis in patients with knee osteoarthritis

Clinical Rheumatology - Central sensitization (CS) is a known contributor to chronic pain in people with knee osteoarthritis (KOA) and is commonly measured by psychophysical testing or...     

Generalisierter Krampfanfall während der Anlage einer axillären Plexusblockade

Die Anaesthesiologie - Eine junge Patientin erleidet während der Anlage einer axillären Plexusblockade einen generalisierten Krampfanfall. Die Mechanismen, im Wesentlichen die vermutlich...     

Influence of Classroom-Level Factors on Implementation Fidelity During Scale-up of Evidence-Based Interventions

Prevention Science - As evidence-based interventions (EBIs) become more widely disseminated, fidelity of implementation (FOI) often wanes. This study explores the association between FOI and...     

Patterns in metabolite profile are associated with risk of more aggressive prostate cancer: A prospective study of 3,057 matched case–control sets from EPIC

Metabolomics may reveal novel insights into the etiology of prostate cancer, for which few risk factors are established. We investigated the association between patterns in baseline plasma metabolite profile and subsequent prostate cancer risk, using data from 3,057 matched case–control sets from the European Prospective Investigation into Cancer and Nutrition (EPIC). We measured 119 metabolite concentrations in plasma samples, collected on average 9.4 years before diagnosis, by mass spectrometry (AbsoluteIDQ p180 Kit, Biocrates Life Sciences AG). Metabolite patterns were identified using treelet transform, a statistical method for identification of groups of correlated metabolites. Associations of metabolite patterns with prostate cancer risk (OR_1SD) were estimated by conditional logistic regression. Supplementary analyses were conducted for metabolite patterns derived using principal component analysis and for individual metabolites. Men with metabolite profiles characterized by higher concentrations of either phosphatidylcholines or hydroxysphingomyelins (OR_1SD = 0.77, 95% confidence interval 0.66–0.89), acylcarnitines C18:1 and C18:2, glutamate, ornithine and taurine (OR_1SD = 0.72, 0.57–0.90), or lysophosphatidylcholines (OR_1SD = 0.81, 0.69–0.95) had lower risk of advanced stage prostate cancer at diagnosis, with no evidence of heterogeneity by follow-up time. Similar associations were observed for the two former patterns with aggressive disease risk (the more aggressive subset of advanced stage), while the latter pattern was inversely related to risk of prostate cancer death (OR_1SD = 0.77, 0.61–0.96). No associations were observed for prostate cancer overall or less aggressive tumor subtypes. In conclusion, metabolite patterns may be related to lower risk of more aggressive prostate tumors and prostate cancer death, and might be relevant to etiology of advanced stage prostate cancer.     

MicroRNA‐204‐5p: A novel candidate urinary biomarker of Xp11.2 translocation renal cell carcinoma

Xp11.2 translocation renal cell carcinoma (Xp11 tRCC) is a rare sporadic pediatric kidney cancer caused by constitutively active TFE3 fusion proteins. Tumors in patients with Xp11 tRCC tend to recur and undergo frequent metastasis, in part due to lack of methods available to detect early‐stage disease. Here we generated transgenic (Tg) mice overexpressing the human PRCC‐TFE3 fusion gene in renal tubular epithelial cells, as an Xp11 tRCC mouse model. At 20 weeks of age, mice showed no histological abnormalities in kidney but by 40 weeks showed Xp11 tRCC development and related morphological and histological changes. MicroRNA (miR)‐204‐5p levels in urinary exosomes of 40‐week‐old Tg mice showing tRCC were significantly elevated compared with levels in control mice. MicroRNA‐204‐5p expression also significantly increased in primary renal cell carcinoma cell lines established both from Tg mouse tumors and from tumor tissue from 2 Xp11 tRCC patients. All of these lines secreted miR‐204‐5p‐containing exosomes. Notably, we also observed increased miR‐204‐5p levels in urinary exosomes in 20‐week‐old renal PRCC‐TFE3 Tg mice prior to tRCC development, and those levels were equivalent to those in 40‐week‐old Tg mice, suggesting that miR‐204‐5p increases follow expression of constitutively active TFE3 fusion proteins in renal tubular epithelial cells prior to overt tRCC development. Finally, we confirmed that miR‐204‐5p expression significantly increases in noncancerous human kidney cells after overexpression of a PRCC‐TFE3 fusion gene. These findings suggest that miR‐204‐5p in urinary exosomes could be a useful biomarker for early diagnosis of patients with Xp11 tRCC.