Long-term complications of continent catheterizable channels: a problem for transitional urologists.

A majority of the transitional urology patient population have neurogenic bladder and many of these patients have undergone creation of continent catheterizable channels (CCCs) to facilitate bladder emptying. Transitional urologists will be faced with revision of these channels due to a variety of possible complications. We performed a comprehensive literature review to the data regarding the incidence, timing, and predisposing factors that lead to complications of CCCs as well as surgical revision techniques and their outcomes. Long-term channel complications and related revisions are common (25-30%) and likely underestimated. While many predictors for revision have been posited, the only predictor that has been significant in robust multivariable analysis is channel type, with appendicovesicostomies having a lower chance of requiring revision compared to Monti channels. Channels created in adults have high likelihood of requiring revision, even within a relatively short follow-up period. We review techniques for management of channel complications and their outcomes. As patients with congenital urologic conditions requiring CCCs are gaining longer lifespans, transitional urologists will be faced with revision and/or replacement of these channels. While some of these patients may require supravesical diversion in the future, data show that revision is feasible with good outcomes. Longer-term follow-up data is needed to understand the life-span and best practices of new CCCs created among the transitional population

NASA Langley's Approach to the Sandia's Structural Dynamics Challenge Problem

The objective of this challenge is to develop a data-based probabilistic model of uncertainty to predict the behavior of subsystems (payloads) by themselves and while coupled to a primary (target) system. Although this type of analysis is routinely performed and representative of issues faced in real-world system design and integration, there are still several key technical challenges that must be addressed when analyzing uncertain interconnected systems. For example, one key technical challenge is related to the fact that there is limited data on target configurations. Moreover, it is typical to have multiple data sets from experiments conducted at the subsystem level, but often samples sizes are not sufficient to compute high confidence statistics. In this challenge problem additional constraints are placed as ground rules for the participants. One such rule is that mathematical models of the subsystem are limited to linear approximations of the nonlinear physics of the problem at hand. Also, participants are constrained to use these models and the multiple data sets to make predictions about the target system response under completely different input conditions. Our approach involved initially the screening of several different methods. Three of the ones considered are presented herein. The first one is based on the transformation of the modal data to an orthogonal space where the mean and covariance of the data are matched by the model. The other two approaches worked solutions in physical space where the uncertain parameter set is made of masses, stiffnesses and damping coefficients; one matches confidence intervals of low order moments of the statistics via optimization while the second one uses a Kernel density estimation approach. The paper will touch on all the approaches, lessons learned, validation 1 metrics and their comparison, data quantity restriction, and assumptions/limitations of each approach. Keywords: Probabilistic modeling, model validation, uncertainty quantification, kernel densit

The burden of chronic ureteral stenting in cervical cancer survivors

ABSTRACT ARTICLE INFO ______________________________________________________________ ______________________ Purpose: Ureteral obstruction in cervical cancer occurs in up to 11% of patients, many of whom undergo ureteral stenting. Our aim was to describe the patient burden of chronic ureteral stenting in a population-based cohort by detailing two objectives: (1) the frequency of repeat procedures for ureteral obstruction; and, (2) the frequency of urinary adverse effects (UAEs) (e.g., lower urinary tract symptoms, flank pain). Materials and Methods: From SEER-Medicare, we identified 202 women who underwent ureteral stent placement prior to or following cervical cancer treatment. The frequency of repeat procedures and rate ratios were compared between treatment modalities. The rates and rate ratios of UAEs were compared between our primary cohort (stent + cervical cancer) and the following groups: no stent + cervical cancer, stent + no cancer, and no stent + no cancer. The "no cancer" group was drawn from the 5% Medicare sample. Results: 117/202 women (58%) underwent >1 stent procedure. The frequency of additional procedures was significantly higher in patients who received radiation as part of their treatment. UAEs were very common in women with stent + cancer. The rate of UTI was 190 (per 100 person-years), 67 for LUTS, 42 for stones, and 6 for flank pain. These rates were 3-10 fold higher than in the no stent + no cancer control group; rates were also higher than in the no stent + cancer and the stent + no cancer women. Conclusions: The burden of disease associated with ureteral stents is higher than expected and urologists should be actively involved in stent management, screening for associated symptoms and offering definitive reconstruction when appropriate

Molecular basis of cobalamin-dependent RNA modification

Queuosine (Q) was discovered in the wobble position of a transfer RNA (tRNA) 47 years ago, yet the final biosynthetic enzyme responsible for Q-maturation, epoxyqueuosine (oQ) reductase (QueG), was only recently identified. QueG is a cobalamin (Cbl)-dependent, [4Fe-4S] cluster-containing protein that produces the hypermodified nucleoside Q in situ on four tRNAs. To understand how QueG is able to perform epoxide reduction, an unprecedented reaction for a Cbl-dependent enzyme, we have determined a series of high resolution structures of QueG from Bacillus subtilis. Our structure of QueG bound to a tRNA[superscript Tyr] anticodon stem loop shows how this enzyme uses a HEAT-like domain to recognize the appropriate anticodons and position the hypermodified nucleoside into the enzyme active site. We find Q bound directly above the Cbl, consistent with a reaction mechanism that involves the formation of a covalent Cbl-tRNA intermediate. Using protein film electrochemistry, we show that two [4Fe-4S] clusters adjacent to the Cbl have redox potentials in the range expected for Cbl reduction, suggesting how Cbl can be activated for nucleophilic attack on oQ. Together, these structural and electrochemical data inform our understanding of Cbl dependent nucleic acid modification.National Science Foundation (U.S.) (MCB 1122977)National Institutes of Health (U.S.) (GM72623 S01, GM120283, and GM17151

Reasons for cessation of clean intermittent catheterization after spinal cord injury: Results from the Neurogenic Bladder Research Group spinal cord injury registry

IntroductionClean intermittent catheterization (CIC) is recommended for bladder management after spinal cord injury (SCI) since it has the lowest complication rate. However, transitions from CIC to other less optimal strategies, such as indwelling catheters (IDCs) are common. In individuals with SCI who stopped CIC, we sought to determine how individual characteristics affect the bladder‐related quality of life (QoL) and the reasons for CIC cessation.MethodsThe Neurogenic Bladder Research Group registry is an observational study, evaluating neurogenic bladder‐related QoL after SCI. From 1479 participants, those using IDC or urinary conduit were asked if they had ever performed CIC, for how long, and why they stopped CIC. Multivariable regression, among participants discontinuing CIC, established associations between demographics, injury characteristics, and SCI complications with bladder‐related QoL.ResultsThere were 176 participants who had discontinued CIC; 66 (38%) were paraplegic and 110 (63%) were male. The most common reasons for CIC cessation among all participants were inconvenience, urinary leakage, and too many urine infections. Paraplegic participants who discontinued CIC had higher mean age, better fine motor scores, and lower educational attainment and employment. Multivariable regression revealed years since SCI was associated with worse bladder symptoms (neurogenic bladder symptom score), ≥4 urinary tract infections (UTIs) in a year was associated with worse satisfaction and feelings about bladder symptoms (SCI‐QoL difficulties), while tetraplegia was associated better satisfaction and feelings about bladder symptoms (SCI‐QoL difficulties).ConclusionsTetraplegics who have discontinued CIC have an improved QoL compared with paraplegics. SCI individuals who have discontinued CIC and have recurrent UTIs have worse QoL.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153674/1/nau24172_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153674/2/nau24172.pd

Speckle Observations of Binary Stars with the WIYN Telescope. III. A Partial Survey of A, F, and G Dwarfs

Two hundred thirty nearby main-sequence stars with spectral types in the range of A to G have been observed by way of speckle interferometry using the WIYN 3.5 m telescope at Kitt Peak, Arizona. The stars had no previous mention of duplicity in the literature. Of those observed, 14 showed clear evidence of a companion, and 63 were classified as suspected nonsingle based on a power spectrum analysis. The remaining stars discussed show no evidence of duplicity to the limit of the detection system in high-quality observations

Predictors of low urinary quality of life in spinal cord injury patients on clean intermittent catheterization

ObjectiveClean intermittent catheterization (CIC) is a preferred method of bladder management for many patients with spinal cord injury (SCI), but long‐term adherence is low. The aim of this study is to identify factors associated with low urinary quality of life (QoL) in SCI adults performing CIC.MethodsOver 1.5 years, 1479 adults with SCI were prospectively enrolled through the Neurogenic Bladder Research Group registry, and 753 on CIC with no prior surgeries were included. Injury characteristics, complications, hand function, and Neurogenic Bladder Symptom Score (NBSS) were analyzed. The NBSS QoL question (overall satisfaction with urinary function) was dichotomized to generate comparative groups (dissatisfied vs neutral/satisfied).ResultsThe cohort was 32.9% female with a median age of 43.2 (18‐86) years, time since the injury of 9.8 (0‐48.2) years, and 69.0% had an injury at T1 or below. Overall 36.1% were dissatisfied with urinary QoL. On multivariable analysis, female gender (odds ratio [OR], 1.63; 95% confidence interval [CI], 1.15‐2.31; P = 0.016), earlier injury (OR, 0.95 per year; 95% CI, 0.93‐0.97; P < 0.001), ≥4 urinary tract infections (UTIs) per year (OR, 2.36; 95% CI, 1.47‐3.81; P = 0.001), and severe bowel dysfunction (OR, 1.42; 95% CI, 1.02‐1.98; P = 0.035) predicted dissatisfaction. Level of injury, fine motor hand function, and caregiver dependence for CIC were not associated with dissatisfaction.ConclusionsIn a mature SCI cohort, physical disability does not predict dissatisfaction with urinary QoL but severe bowel dysfunction and recurrent UTIs have a significant negative impact. With time the rates of dissatisfaction decline but women continue to be highly dissatisfied on CIC and may benefit from early intervention to minimize the burden of CIC on urinary QoL.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149763/1/nau23983.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149763/2/nau23983_am.pd

Non-thermal Plasma Exposure Rapidly Attenuates Bacterial AHL-Dependent Quorum Sensing and Virulence.

The antimicrobial activity of atmospheric pressure non-thermal plasma has been exhaustively characterised, however elucidation of the interactions between biomolecules produced and utilised by bacteria and short plasma exposures are required for optimisation and clinical translation of cold plasma technology. This study characterizes the effects of non-thermal plasma exposure on acyl homoserine lactone (AHL)-dependent quorum sensing (QS). Plasma exposure of AHLs reduced the ability of such molecules to elicit a QS response in bacterial reporter strains in a dose-dependent manner. Short exposures (30–60 s) produce of a series of secondary compounds capable of eliciting a QS response, followed by the complete loss of AHL-dependent signalling following longer exposures. UPLC-MS analysis confirmed the time-dependent degradation of AHL molecules and their conversion into a series of by-products. FT-IR analysis of plasma-exposed AHLs highlighted the appearance of an OH group. In vivo assessment of the exposure of AHLs to plasma was examined using a standard in vivo model. Lettuce leaves injected with the rhlI/lasI mutant PAO-MW1 alongside plasma treated N-butyryl-homoserine lactone and n-(3-oxo-dodecanoyl)-homoserine lactone, exhibited marked attenuation of virulence. This study highlights the capacity of atmospheric pressure non-thermal plasma to modify and degrade AHL autoinducers thereby attenuating QS-dependent virulence in P. aeruginosa

Contemporary multicenter outcomes of continent cutaneous ileocecocystoplasty in the adult population over a 10-year period: A Neurogenic Bladder Research Group study

AIMS: Evidence is sparse on the long-term outcomes of continent cutaneous ileocecocystoplasty (CCIC). We hypothesized that obesity, laparoscopic/robotic approach, and concomitant surgeries would affect morbidity after CCIC and aimed to evaluate the outcomes of CCIC in adults in a multicenter contemporary study. METHODS: We retrospectively reviewed the charts of adult patients from sites in the Neurogenic Bladder Research Group undergoing CCIC (2007-2017) who had at least 6 months of follow-up. We evaluated patient demographics, surgical details, 90-day complications, and follow-up surgeries. the Mann-Whitney U test was used to compare continuous variables and χ² and Fisher\u27s Exact tests were used to compare categorical variables. RESULTS: We included 114 patients with a median age of 41 years. The median postoperative length of stay was 8 days. At 3 months postoperatively, major complications occurred in 18 (15.8%), and 24 patients (21.1%) were readmitted. During a median follow-up of 40 months, 48 patients (42.1%) underwent 80 additional related surgeries. Twenty-three patients (20.2%) underwent at least one channel revision, most often due to obstruction (15, 13.2%) or incontinence (4, 3.5%). Of the channel revisions, 10 (8.8%) were major and 14 (12.3%) were minor. Eleven patients (9.6%) abandoned the catheterizable channel during the follow-up period. Obesity and laparoscopic/robotic surgical approach did not affect outcomes, though concomitant surgery was associated with a higher rate of follow-up surgeries. CONCLUSIONS: In this contemporary multicenter series evaluating CCIC, we found that the short-term major complication rate was low, but many patients require follow-up surgeries, mostly related to the catheterizable channel

Ultrasound Mediated Gemcitabine Delivery Reduces the Normal-Tissue Toxicity of Chemoradiation Therapy in a Muscle-Invasive Bladder Cancer Model

Purpose: Chemoradiation is the standard of care in muscle-invasive bladder. While agents such as gemcitabine can enhance tumour radiosensitisation, their side effects can limit patient eligibility and treatment efficacy. Here we investigate ultrasound and microbubbles for targeting gemcitabine delivery to reduce normal tissue toxicity in a murine orthotopic MIBC model. Materials and Methods: CD1-nude mice were injected orthotopically with RT112 bladder tumour cells. Conventional chemoradiation involved injecting gemcitabine (10 mg/kg) before 6 Gy targeted irradiation of the bladder area using a Small Animal Radiation Research Platform (SARRP). Ultrasound-mediated gemcitabine delivery (10 mg/kg gemcitabine) involved either co-administration of microbubbles with gemcitabine or conjugating gemcitabine onto microbubbles followed by exposure to ultrasound (1.1 MHz centre frequency, 1 MPa peak negative pressure, 1% duty cycle and 0.5 Hz pulse repetition frequency), prior to SARRP irradiation. The effect of ultrasound and microbubbles alone was also tested. Tumour volumes were measured by 3D ultrasound imaging. Acute normal tissue toxicity from 12 Gy to the lower bowel area was assessed using an intestinal crypt assay in mice culled. 3.75 days post-treatment. Results: Significant tumour growth delay was observed with conventional chemoradiation and both microbubble groups (p Conclusions: Ultrasound and microbubbles offer a promising new approach for improving chemoradiation therapy in muscle-invasive bladder cancer, maintaining tumour growth delay but with reduced acute intestinal toxicity compared to conventional chemoradiation therapy.</p