Development of an isoform-specific gene suppression system: the study of the human Pax-5B transcriptional element

The transcription factor Pax-5, is vital during B lymphocyte differentiation and is known to contribute to the oncogenesis of certain cancers. The Pax-5 locus generates multiple yet structurally related mRNA transcripts through the specific activation of alternative promoter regions and/or alternative splicing events which poses challenges in the study of specific isoform function. In this study, we investigated the function of a major Pax-5 transcript, Pax-5B using an enhanced version of the Hepatitis Delta Virus ribozyme (HDV Rz) suppression system that is specifically designed to recognize and cleave the human Pax-5B mRNA. The activity of these ribozymes resulted in the specific suppression of the Pax-5B transcripts without altering the transcript levels of other closely related Pax-5 isoforms mRNAs both in vitro and in an intracellular setting. Following stable transfection of the ribozymes into a model B cell line (REH), we showed that Pax-5B suppression led to an increase of CD19 mRNA and cell surface protein expression. In response to this Pax-5B specific deregulation, a marked increase in apoptotic activity compared to control cell lines was observed. These results suggest that Pax-5B has distinct roles in physiological processes in cell fate events during lymphocyte development

Freezing of gait and fall detection in Parkinson’s disease using wearable sensors:a systematic review

Despite the large number of studies that have investigated the use of wearable sensors to detect gait disturbances such as Freezing of gait (FOG) and falls, there is little consensus regarding appropriate methodologies for how to optimally apply such devices. Here, an overview of the use of wearable systems to assess FOG and falls in Parkinson’s disease (PD) and validation performance is presented. A systematic search in the PubMed and Web of Science databases was performed using a group of concept key words. The final search was performed in January 2017, and articles were selected based upon a set of eligibility criteria. In total, 27 articles were selected. Of those, 23 related to FOG and 4 to falls. FOG studies were performed in either laboratory or home settings, with sample sizes ranging from 1 PD up to 48 PD presenting Hoehn and Yahr stage from 2 to 4. The shin was the most common sensor location and accelerometer was the most frequently used sensor type. Validity measures ranged from 73–100% for sensitivity and 67–100% for specificity. Falls and fall risk studies were all home-based, including samples sizes of 1 PD up to 107 PD, mostly using one sensor containing accelerometers, worn at various body locations. Despite the promising validation initiatives reported in these studies, they were all performed in relatively small sample sizes, and there was a significant variability in outcomes measured and results reported. Given these limitations, the validation of sensor-derived assessments of PD features would benefit from more focused research efforts, increased collaboration among researchers, aligning data collection protocols, and sharing data sets

Ileus and small bowel obstruction after radical cystectomy for bladder cancer: Analysis from the Nationwide Inpatient Sample.

PURPOSE: To investigate prevalence and predictors of postoperative small bowel obstruction (SBO) and ileus in a large cohort of bladder cancer (BCa) patients treated with radical cystectomy (RC). METHODS: All patients within the Nationwide Inpatient Sample who underwent RC for BCa between 2006 and 2012 were identified. First, prevalence of SBO and ileus was analyzed. Second, predictors of these bowel-related complications were identified using multivariable regression analyses. Third, the association between SBO, ileus, and length of stay was evaluated using logistic regression models adjusted for clustering. Prolonged length of stay was defined as hospital stay above mean stay of the population (\u3e10 days). Fourth, the effect of SBO and ileus on mean inpatient cost of healthcare was examined. RESULTS: Of overall 41,498 patients, 1071 (2.6%) experienced SBO, and 11,155 (26.9%) experienced ileus. Predictors of ileus included age, male gender, black race, hospital characteristics, anemia, chronic pulmonary disease, drug abuse, hypothyroidism, fluid and electrolyte disorders, and neurological disorders (all p \u3c 0.05) Predictors of SBO included male gender, Asian/Pacific islander race, hospital characteristics, congestive heart failure, fluid and electrolyte disorders, and psychosis (all p \u3c 0.05). . Postoperative SBO (odds ratio (OR) 19.587; 95% confidence interval (CI):15.869-24.167) and ileus (OR 5.646; 95% CI:5.336-5.974) were associated with prolonged length of stay (all p \u3c 0.001).Median cost of hospital stay was $56.315 for patients who developed SBO,$32,472 for patients who developed ileus, and $24,600 for patients after cystectomy without ileus or SBO. CONCLUSIONS: Significant prevalence of bowel-related complications in patients after RC was observed. These complications are strongly associated with prolonged length of stay and higher healthcare cost. Increasing awareness of SBO and ileus, identification of patients at risk prior to surgery, and implementation of protective strategies are strongly indicated in cystectomy patients.

"Geist ist wesentlich Form." Benses Stilbegriffe

Der Stilbegriff in seinem Verhältnis zum Denken und Schreiben spielt zweifellos eine zentrale Rolle in Benses Philosophie. Zeit seines Lebens vertrat er jedoch sehr unterschiedliche Stilbegriffe, eher konventionelle und andere von befremdlicher Eigentümlichkeit. In diesem Essay sollen die Wandlungen des Stilbegriffs bei Bense in einem locker an der Chronologie orientierten Überblick vorgeführt und die argumentativen Kontexte für die jeweiligen Modifikationen skizziert und beurteilt werden