OBJECTIVES Dysbiosis leading to abnormal intestinal fermentation has been suggested as a possible etiological mechanism in irritable bowel syndrome (IBS). We aimed to investigate the location and magnitude of altered intestinal bacterial fermentation in IBS and its clinical subtypes. METHODS One hundred fourteen IBS patients who satisfied Rome III criteria and 33 healthy controls (HC) were investigated. Intestinal fermentation was assessed using two surrogate measures: intestinal intraluminal pH and fecal short chain fatty acids (SCFAs). Intraluminal pH and intestinal transit time were measured in the small and large bowel using a wireless motility capsule (SmartPill™) in 47 IBS and 10 HC. Fecal SCFAs including acetate, propionate, butyrate and lactate were analyzed by capillary gas chromatography in all enrolled subjects. Correlations between intestinal pH, fecal SCFAs, intestinal transit time and IBS symptom scores were analyzed. RESULTS Colonic intraluminal pH levels were significantly lower in IBS patients compared to HC (total colonic pH, 6.8 for IBS vs. 7.3 for HC, P = 0.042). There were no differences in total and segmental pH levels in the small bowel between IBS patients and HC (6.8 vs. 6.8, P = NS). The intraluminal colonic pH differences were consistent in all IBS subtypes. Total SCFAs level was significantly lower in C-IBS patients than in D-IBS and M-IBS patients and HC. The total SCFAs level in all IBS subjects was similar with that of HC. Colonic pH levels correlated positively with colon transit time (CTT) and IBS symptoms severity. Total fecal SCFAs levels correlated negatively with CTT, and positively with stool frequency. CONCLUSIONS Colonic intraluminal pH is decreased, suggesting higher colonic fermentation, in IBS patients compared with HC. Fecal SCFAs are not a sensitive marker to estimate intraluminal bacterial fermentation.

AMLPS identified patients with a poor DFS and OS, and it was independent of age, pathologic stage, and various inflammatory markers.

Genomic alterations involving translocations of the ETS-related gene ERG occur in approximately half of prostate cancer cases. These alterations result in aberrant, androgen-regulated production of ERG protein variants that directly contribute to disease development and progression. This study describes the discovery and characterization of a new class of small molecule ERG antagonists identified through rational in silico methods. These antagonists are designed to sterically block DNA binding by the ETS domain of ERG and thereby disrupt transcriptional activity. We confirmed the direct binding of a lead compound, VPC-18005, with the ERG-ETS domain using biophysical approaches. We then demonstrated VPC-18005 reduced migration and invasion rates of ERG expressing prostate cancer cells, and reduced metastasis in a zebrafish xenograft model. These results demonstrate proof-of-principal that small molecule targeting of the ERG-ETS domain can suppress transcriptional activity and reverse transformed characteristics of prostate cancers aberrantly expressing ERG. Clinical advancement of the developed small molecule inhibitors may provide new therapeutic agents for use as alternatives to, or in combination with, current therapies for men with ERG-expressing metastatic castration-resistant prostate cancer.

Three dimensional PD-US was a useful and effective method for assessing endometrial blood flow in IVF cycles. Good endometrial blood flow on the day of embryo transfer might be associated with high pregnancy success with a GnRH long protocol, because this is indicative of endometrial receptivity in fresh IVF cycles.

3D-TVUS assessment of the uterus provides an accurate depiction of adhesion and extent of cavity damage in patients with suspected IUA.