Retrograde intrarenal surgery (RIRS) is highly successful at eliminating renal stones of various sizes and compositions. As urologists are taking on more complex procedures using RIRS, this has led to an increase in operative (OR) times. Our objective was to determine the best predictor of OR time in patients undergoing RIRS. We retrospectively reviewed the records of patients undergoing unilateral RIRS for solitary stones over a 10 year time span. Stones were fragmented and actively extracted using a basket. Variables potentially affecting OR time such as patient age, sex, BMI, lower pole stone location, volume, Hounsfield units (HU), composition, ureteral access sheath (UAS) use, and pre-operative stenting were collected. Multivariable linear and stepwise regression was used to evaluate the predictors of OR time. There were 118 patients that met inclusion criteria. The median stone volume was 282.6 mm (IQR 150.7-644.7) and the mean OR time was 50 min (±25.9 SD). On univariate linear regression, stone volume had a moderate correlation with OR time (y = 0.022x + 38.2, r = 0.363, p< 0.01). On multivariable stepwise regression, stone volume had the strongest impact on OR time, increasing time by 2.0 min for each 100 mm increase in stone volume (p < 0.001). UAS added 13.5 (SE 3.9, p = 0.001) minutes and renal lower pole location added 9 min (SE 4.3, p = 0.03) in each case they were used. Pre-operative stenting, HU, calcium oxalate stone composition, sex, and age had no significant effect on OR time. Amongst the main stone factors in RIRS, stone volume has the strongest impact on operative time. This can be used to predict the length of the procedure by roughly adding 2 min per 100 mm increase in stone volume.

Pelvic floor disorders encompass abnormalities of urination, defecation, sexual function, pelvic organ prolapse, and chronic pain, and can have significant quality of life implications for patients. Current guidelines recommend behavioral modifications and conservative treatments as first-line therapy for pelvic floor disorders. We have reviewed the literature for articles published on physical, complementary, and alternative treatments for pelvic floor disorders over the past 5 years. Review of pelvic floor muscle physiotherapy (PFMT) and biofeedback (BF) shows a benefit for patients suffering from bladder dysfunction (incontinence, overactive bladder), bowel dysfunction (constipation, fecal incontinence), pelvic organ prolapse, and sexual dysfunction (pelvic pain). Combination of PFMT and BF has shown improved results compared to PFMT alone, and some studies find that electrical stimulation can augment the benefit of BF and PFMT. Additionally, acupuncture and cognitive behavioral therapy has shown to be an effective treatment for pelvic floor disorders, particularly with respect to pelvic pain. This update highlights beneficial conservative treatments available for pelvic floor dysfunction, and supplements the current literature on treatment options for patients suffering from these disorders.

Protein phosphatase magnesium-dependent-1A (PPM1A) dephosphorylates SMAD2/3, which suppresses TGF-β signaling in keratinocytes and during Xenopus development; however, potential involvement of PPM1A in chronic kidney disease is unknown. PPM1A expression was dramatically decreased in the tubulointerstitium in obstructive and aristolochic acid nephropathy, which correlates with progression of fibrotic disease. Stable silencing of PPM1A in human kidney-2 human renal epithelial cells increased SMAD3 phosphorylation, stimulated expression of fibrotic genes, induced dedifferentiation, and orchestrated epithelial cell-cycle arrest via SMAD3-mediated connective tissue growth factor and plasminogen activator inhibitor-1 up-regulation. PPM1A stable suppression in normal rat kidney-49 renal fibroblasts, in contrast, promoted a SMAD3-dependent connective tissue growth factor and plasminogen activator inhibitor-1-induced proliferative response. Paracrine factors secreted by PPM1A-depleted epithelial cells augmented fibroblast proliferation (>50%) compared with controls. PPM1A suppression in renal cells further enhanced TGF-β1-induced SMAD3 phosphorylation and fibrotic gene expression, whereas PPM1A overexpression inhibited both responses. Moreover, phosphate tensin homolog on chromosome 10 depletion in human kidney-2 cells resulted in loss of expression and decreased nuclear levels of PPM1A, which enhanced SMAD3-mediated fibrotic gene induction and growth arrest that were reversed by ectopic PPM1A expression. Thus, phosphate tensin homolog on chromosome 10 is an upstream regulator of renal PPM1A deregulation. These findings establish PPM1A as a novel repressor of the SMAD3 pathway in renal fibrosis and as a new therapeutic target in patients with chronic kidney disease.-Samarakoon, R., Rehfuss, A., Khakoo, N. S., Falke, L. L., Dobberfuhl, A. D., Helo, S., Overstreet, J. M., Goldschmeding, R., Higgins, P. J. Loss of expression of protein phosphatase magnesium-dependent 1A during kidney injury promotes fibrotic maladaptive repair.

The decreased blood flow associated with increased oxidative damage demonstrates that cyclical damage to cellular membranes occurs. This supports the hypothesis that cycling estrogen may play a role in the etiology of LUTD of women.

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OBJECTIVE To investigate the effect of letrozole (a potent aromatase inhibitor that effectively inhibit the synthesis of oestrogen) on bladder contraction with changes in morphology and biochemistry. MATERIALS AND METHODS Sixteen female New Zealand white rabbits were separated into four equal groups; groups 1–3 were given oral letrozole for 1, 2 and 3 weeks, and group 4 was given saline and served as the control group. At the end of the medication period each rabbit was anaesthetized and the bladder muscle strips were used for contractile, histological and biochemical studies. RESULTS The concentration of serum oestrogen was significantly lower and testosterone was significantly higher in letrozole‐treated rabbits than in the control group. The rabbits treated for 1 week with letrozole showed significant decreases in the contractile responses to electrical field stimulation, ATP and carbachol, but not to KCl. Contractility returned to normal in the rabbits treated for 2 and 3 weeks. Letrozole resulted in an increased volume percentage of collagens and decreased bladder compliance. The volume percentage of the smooth muscle component also changed, with a significant decrease at 1 week and then a gradual increase at 2 and 3 weeks. Contractile dysfunction was absent at 2 and 3 weeks, which was consistent with no change in sarcoplasmic reticulum Ca2+‐ATPase content or mitochondrial function. CONCLUSIONS The bladder contractility decline in the first week and was restored at 2 and 3 weeks. The present study unexpectedly showed the possibility that testosterone might be as important as oestrogen in the contractile function of the female bladder.

Objectives-The objective of these studies was to determine the efficacy of coenzyme Q10 (CoQ 10) and α-lipoic acid (α-LA), either alone or in combination, to protect the contractile responses of the rabbit urinary bladder from damage caused by repetitive stimulation in the presence or absence of in vitro ischemia.Methods-Four groups of New Zealand White rabbits (N=4 per group) were treated with vehicle (group 1), CoQ 10 (group 2), α-LA (group 3), or CoQ 10 + α-LA (group 4) for 2 weeks. At the end of the treatment period, eight longitudinal strips from each rabbit bladder body were placed in oxygenated Tyrode's solution with glucose (normal physiological medium). Strips were stimulated by field stimulation (FS), carbachol, and KCl, and the responses were recorded. One half the strips were switched for 1 hour to Tyrode's with no glucose equilibrated with nitrogen (ischemia medium). Simultaneously, all strips were subjected to 1 h of repetitive FS (RS) followed by 1 h of recovery in normal physiological medium and the responses to all stimuli were recorded again.Results-CoQ 10 showed no protective effect. α-LA resulted in increased contractile responses of the control bladder and showed a moderate protective effect for all forms of stimulation. The combination however, showed a significantly greater increased in the contraction of control bladder and a greater protective effect than α-LA alone Conclusion-The combination of α-LA and CoQ10 treatment both enhanced contractile response in normal medium, and diminished contractile dysfunction induced by RS and ischemia.

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