Efficacy of transcutaneous posterior tibial nerve stimulation in children with functional voiding disorders.

AIMS: To assess the efficacy of transcutaneous posterior tibial nerve stimulation (TPTNS) on functional voiding disorder (FVD) and investigate the utility of urine biomarkers (UBs: nerve growth factor, transforming growth factor-beta 1, and tissue inhibitor of metalloproteinases 2) in diagnosis and follow-up. METHODS: A total of 44 children were included to this randomized controlled trial prospectively. After randomization, 20 of 30 children with storage phase dysfunction those were unresponsive or noncompliant to medical treatment received TPTNS treatment (test group) and 10 children underwent TPTNS with no current (sham group) for 12 weeks. Fourteen healthy children constituted the nonsymptomatic group. UB levels, dysfunctional voiding and incontinence scoring system (DVISS), voiding diary, and quality of life (QoL) scores were assessed before and after treatment in the treatment groups. RESULTS: QoL scores, overall and day-time DVISS scores were significantly decreased in both sham and test groups (p < 0.05). In addition to these findings, the frequency of incontinence and urgency episodes were also significantly reduced (p < 0.05) in the TPTNS treatment group. This effect in the test group was still valid 2 years after intervention. There was no significant difference in UBs measurements between treatment and nonsymptomatic groups and between pretreatment and posttreatment measurements of test and sham groups. CONCLUSIONS: TPTNS is an efficient minimally invasive treatment in children with FVD who do not respond to medical treatment. TPTNS provides a significant improvement on episodes of frequency, episodes of incontinence, overall and day-time DVISS scores, and QoL scores. The effectiveness of treatment continues even at the end of the second year of intervention. UBs were not found to be predictive in terms of diagnosis and evaluating the treatment response.

Joint Modeling Approach on Evaluating Time-Dependent CutOff Values for C-Reactive Protein in Mixed Intensive Care Unit Population.

BACKGROUND: Serial C-reactive protein (CRP) biomarker values are frequently recorded from patients in adult intensive care units (ICU). The aim of this study was to assess the time-dependent diagnostic accuracy of repeated CRP measurements in predicting ICU mortality and determine the time-dependent cutoff values for this biomarker in mixed ICU population. METHODS: Joint modeling was performed to model repeated CRP measurements and survival data. Time-dependent AUC (td-AUC) values were used to assess the diagnostic performances. Maximization of the product of sensitivity and specificity rule was applied to determine the time-dependent cutoff values. RESULTS: Time-dependent diagnostic performance of serial CRP values were found as moderate in overall, observed to be higher in males than females, ranging from 0.603 to 0.624 in females and 0.639 to 0.690 in males. On the other hand, time-dependent cutoff values either remained constant or decreased through the 3rd day after the last measurement for both gender groups. CONCLUSIONS: Newly proposed time-dependent cutoff values for CRP biomarker are suggested to be used in clinics to discriminate subjects who are at risk and who are not during the first three days after the last measurement. Furthermore, taking serial CRP values in predicting the risk of death at ICU is highly recommended, to be able to assess the change in longitudinal profiles of subjects throughout the follow-up period.

The effect of telomerase template antagonist GRN163L on bone-marrow-derived rat mesenchymal stem cells is reversible and associated with altered expression of cyclin d1, cdk4 and cdk6.

Telomerase activity is essential for the continued growth and survival of malignant cells, therefore inhibition of this activity presents an attractive target for anti-cancer therapy. The telomerase inhibitor GRN163L, was shown to inhibit the growth of cancer cells both in vitro and in vivo. Mesenchymal stem cells (MSCs) also show telomerase activity in maintaining their self-renewal; therefore the effects of telomerase inhibitors on MSCs may be an issue of concern. MSCs are multipotent cells and are important for the homeostasis of the organism. In this study, we sought to demonstrate in vitro effects of GRN163L on rat MSCs. When MSCs were treated with 1 microM GRN163L, their phenotype changed from spindle-shaped cells to rounded ones and detached from the plate surface, similar to cancer cells. Quantitative-RT-PCR and immunoblotting results revealed that GRN163L holds MSCs at the G1 state of the cell cycle, with a drastic decrease in mRNA and protein levels of cyclin D1 and its cdk counterparts, cdk4 and cdk6. This effect was not observed when MSCs were treated with a mismatch control oligonucleotide. One week after GRN163L was removed, mRNA and protein expressions of the genes, as well as the phenotype of MSCs returned to those of untreated cells. Therefore, we concluded that GRN163L does not interfere with the self-renewal and differentiation of MSCs under short term in vitro culture conditions. Our study provides additional support for treating cancers by administrating GRN163L without depleting the body's stem cell pools.