MicroRNA profile in stage I clear cell renal cell carcinoma predicts progression to metastatic disease.

OBJECTIVE: This study sought to identify microRNA (miRNA) profiles of small, pathologically confirmed stage 1 clear cell renal cell carcinoma (ccRCC) tumors that are associated with progression to metachronous metastatic disease. MATERIALS AND METHODS: Fifty-five pathologic stage 1 ccRCC tumors ≤5cm, from 2 institutions, were examined in a miRNA screening, followed by a validation study. For the screening phase 752 miRNA were evaluated on each sample to identify those with differential expression between tumors that subsequently did (n = 10) or did not (n = 10) progress to metastatic disease. For the validation, 35 additional samples (20 nonprogressors and 15 with distant progression) were utilized to investigate 20 miRNA to determine if a miRNA panel could differentiate aggressive tumors: associations of miRNA expression with cancer specific survival was also investigated. RESULTS: In the screening analysis, 35 miRNA were differentially expressed (P < 0.05, FDR < 0.1) between the groups. In the validation, 11 miRNA were confirmed to have differential expression. The miRNA -10a-5p, -23b-3p, and -26a-5p differentiated nonprogressive and distant progressive disease with a sensitivity of 73.3% and a specificity of 85% (AUC=0.893). In addition, levels of miR-30a-3p and -145-5p were identified as independent prognostic factors of cancer specific survival. CONCLUSIONS: This investigation identified miRNA biomarkers that may differentiate between non-progressive ccRCC tumors and those that progress to metastatic disease in this group of stage I tumors. The miRNA profiles determined in this study have the potential to identify patients with small renal masses who are likely to have progressive ccRCC. Such information may be valuable to incorporate into predictive models.

Conservative Management of Urinary Incontinence in Women.

Urinary incontinence in women has a high prevalence and causes significant morbidity. Given that urinary incontinence is not generally a progressive disease, conservative therapies play an integral part in the management of these patients. We conducted a nonsystematic review of the literature to identify high-quality studies that evaluated the different components of conservative management of stress urinary incontinence, including behavioral therapy, bladder training, pelvic floor muscle training, lifestyle changes, mechanical devices, vaginal cones, and electrical stimulation. Urinary incontinence can have a severe impact on our healthcare system and patients' quality of life. There are currently a wide variety of treatment options for these patients, ranging from conservative treatment to surgical treatment. Although further research is required in the area of conservative therapies, nonsurgical treatments are effective and are preferred by some patients.

Variation in enkephalin immunoreactivity in the social behavior network and song control system of male European starlings (Sturnus vulgaris) is dependent on breeding state and gonadal condition.

Many temperate zone songbird species exhibit marked seasonal variation in song quality as well as in the motivation to sing. Two brain systems are known to mediate such annual variation in song quality and motivation: (1) the song control system (SCS), and (2) the social behavior network (SBN), respectively. How these two circuits interact to produce changes in singing behavior is not well understood. The opioid enkephalin is expressed in both the SCS and SBN and may function to modulate song quality in a socially relevant manner. Using immunocytochemistry, we examined variation in enkephalin immunoreactivity (ENK-ir) in male European starlings (Sturnus vulgaris) that were in breeding conditions (i.e. photostimulated) or non-breeding conditions (i.e. photorefractory). We also included a group of castrated photostimulated males to investigate the relationship between gonadal steroids and ENK-ir. ENK-ir in the preoptic area (POA) and lateral septum (LS) was greater in photostimulated intact birds as compared to photorefractory males, but not in other regions within the SBN. There was a significant difference in ENK-ir in two forebrain song nuclei, HVC and the lateral nucleus of the anterior medial nidopallium (lMAN), with lower expression in photostimulated intact as compared to photorefractory birds. ENK-ir did not change across breeding conditions in the Nucleus Interface (NIf). After accounting for the volumetric change in HVC and lMAN, the pattern of ENK-ir remained greater in photorefractory compared to intact photostimulated starlings. We propose that the observed regulation of ENK-ir in the POA and LS may be related to seasonal changes in the motivation to engage in singing behavior, while the change in ENK-ir in the song system are associated with the quality of the song produced. Thus seasonal changes in a single neuromodulatory system can have very different functional effects based on the neuroanatomical specificity of its expression.