The combined serum levels of miR-375 and urokinase plasminogen activator receptor are suggested as diagnostic and prognostic biomarkers in prostate cancer.

This study aimed to assess the applicability of miR-375 in combination with the soluble urokinase plasminogen activator receptor (suPAR) protein as a diagnostic and/or prognostic biomarker for prostate cancer (PCa) patients. miR-375 levels by qRT-PCR and suPAR levels by ELISA were evaluated in serum samples from 146 PCa patients, 35 benign prostate hyperplasia (BPH) patients and 18 healthy controls. Antigen levels of suPAR differed between healthy controls and PCa or BPH patients, whereas miR-375 levels differed between PCa and BPH patients or healthy controls (p < 0.001). Additionally, suPAR levels differed between the Gleason sum groups GS = 7 versus GS > 7, with higher levels in the latter group (p = 0.011), and miR-375 levels were higher in the tumor stage group T3-T4 compared with the T1-T2 group (p = 0.039). A high concentration of suPAR was associated with a poor disease-specific survival (DSS; p = 0.039). The combination of suPAR and miR-375 levels identified a patient group possessing high levels for both parameters. This was associated with a poorer 10-year overall survival (OS) and DSS, with a 6.38-fold increased risk of death and a 7.68-fold increased risk of tumor-related death (p = 0.00026 and p = 0.014; univariate Cox's regression analysis). In a multivariate Cox's regression analysis PCa patients with high levels of suPAR and miR-375 showed a 5.72-fold increased risk of death in OS (p = 0.006). In summary, the differences between the PCa/BPH/healthy control cohorts for either suPAR and miR-375 levels in conjunction with the association of combined high suPAR/miR-375 levels with a poor prognosis suggest a diagnostic and prognostic impact for PCa patients.

Quantification of Nighttime Micturition With an Ambulatory Sensor-Based System.

Among elderly males, benign prostate syndrome (BPS) is the most common urinary disorder. Nocturia is one of the major symptoms of BPS and has a considerable influence on the quality of life. For assessment of BPS (including nocturia), the International Prostate Symptom Score is widely used, but questionnaires are prone to bias. To date, there is no objective measurement system available for nocturia. In this study, we present an unobtrusive and nonstigmatizing device for objective measurement of nighttime micturition. In a preliminary study of six males diagnosed with BPS and nighttime micturition ≥ 2×, we showed that the device is accurate, with an average misdetection rate of 0.32 events and a mean absolute deviation of 3.8% when comparing the average number of nighttime micturition occurrences. In this extended study, an additional nine males were recorded and data from an occupancy sensor were also included. The results of the preliminary study were confirmed with an average misdetection rate of 0.33 events and a mean absolute deviation of 9.1%. The system can, therefore, be used to objectively measure nighttime micturition and, thereby, provide the basis for treatment, e.g., medication efficacy assessment.

An ambulatory sensor-based system for quantification of nighttime micturition for accurate nocturia assessment.

Nocturia is a widespread condition where patients need to micturate frequently during the nighttime. In order to define treatment and measure therapeutic success in nocturia, questionnaires are traditionally used for ambulatory assessment. However, questionnaires were reported to suffer from compliance, embarrassment and subjective bias. An automatic sensor-based system for quantification of nighttime micturition for accurate nocturia assessment would not suffer from these disadvantages, and its development was therefore the purpose of this study. We defined a sensor-based system for ambulatory use, consisting of a sensor watch and a room occupancy sensor. Using this system, we so far collected data from 6 participants and 82 nights in an ongoing study. We report the details of the system, as well as the data analysis. The system is very accurate, with an average misdetection rate of 0.32 and a mean absolute deviation of 3.8 % when comparing the average number of nighttime micturitions. This novel sensor-based nighttime micturition quantification system has the potential to be used as an objective ambulatory assessment tool for nocturia diagnosis and treatment.

Tetracycline inducible gene manipulation in serotonergic neurons.

The serotonergic (5-HT) neuronal system has important and diverse physiological functions throughout development and adulthood. Its dysregulation during development or later in adulthood has been implicated in many neuropsychiatric disorders. Transgenic animal models designed to study the contribution of serotonergic susceptibility genes to a pathological phenotype should ideally allow to study candidate gene overexpression or gene knockout selectively in serotonergic neurons at any desired time during life. For this purpose, conditional expression systems such as the tet-system are preferable. Here, we generated a transactivator (tTA) mouse line (TPH2-tTA) that allows temporal and spatial control of tetracycline (Ptet) controlled transgene expression as well as gene deletion in 5-HT neurons. The tTA cDNA was inserted into a 196 kb PAC containing a genomic mouse Tph2 fragment (177 kb) by homologous recombination in E. coli. For functional analysis of Ptet-controlled transgene expression, TPH2-tTA mice were crossed to a Ptet-regulated lacZ reporter line (Ptet-nLacZ). In adult double-transgenic TPH2-tTA/Ptet-nLacZ mice, TPH2-tTA founder line L62-20 showed strong serotonergic ß-galactosidase expression which could be completely suppressed with doxycycline (Dox). Furthermore, Ptet-regulated gene expression could be reversibly activated or inactivated when Dox was either withdrawn or added to the system. For functional analysis of Ptet-controlled, Cre-mediated gene deletion, TPH2-tTA mice (L62-20) were crossed to double transgenic Ptet-Cre/R26R reporter mice to generate TPH2-tTA/Ptet-Cre/R26R mice. Without Dox, 5-HT specific recombination started at E12.5. With permanent Dox administration, Ptet-controlled Cre-mediated recombination was absent. Dox withdrawal either postnatally or during adulthood induced efficient recombination in serotonergic neurons of all raphe nuclei, respectively. In the enteric nervous system, recombination could not be detected. We generated a transgenic mouse tTA line (TPH2-tTA) which allows both inducible and reversible transgene expression and inducible Cre-mediated gene deletion selectively in 5-HT neurons throughout life. This will allow precise delineation of serotonergic gene functions during development and adulthood.