Dyslipidemia and kidney stone risk.

PURPOSE: We studied the impact of dyslipidemia on 24-hour urinalysis and stone composition. MATERIALS AND METHODS: We retrospectively identified patients with nephrolithiasis who underwent 24-hour urinalysis and lipid profile evaluation within 3 months. Patients were divided into groups based on total cholesterol, high density lipoprotein, nonhigh density lipoprotein and triglycerides. The groups were compared based on demographic data, diabetes, hypertension and each component of 24-hour urinalysis and stone composition. Multivariate analysis and linear regression were performed to control for potential confounders, including age, gender, body mass index, diabetes and hypertension. RESULTS: A total of 2,442 patients with a mean age of 51.1 years were included in study. On multivariate analysis patients with high total cholesterol had significantly higher urinary potassium and calcium, those with low high density lipoprotein or high triglycerides had significantly higher urinary sodium, oxalate and uric acid with lower pH, and those with high nonhigh density lipoprotein had higher urinary sodium and uric acid. Regarding stone composition, high total cholesterol and triglycerides were significantly associated with a higher uric acid stone rate (p = 0.006 and <0.001, respectively). Linear regression showed a significant association of nonhigh density lipoprotein with higher urinary sodium (p = 0.011) and uric acid (p <0.001) as well as triglycerides and higher uric acid (p = 0.017), and lower urinary pH (p = 0.005). CONCLUSIONS: There is a link between dyslipidemia and kidney stone risk that is independent of other components of metabolic syndrome such as diabetes and obesity. Specific alterations in the patient lipid profiles may portend unique aberrations in urine physicochemistry and stone risk.

Ureteric wall thickness as a novel predictor for failed retrograde ureteric stent placement.

INTRODUCTION: We sought to identify predictors of failed retrograde ureteric stent (FRS) placement in the setting of obstructing ureteric calculi. In addition to patient- and stone-specific characteristics, we also considered computed tomography (CT) measures of ureteric wall thickness (UWT), as it has shown clinical potential in predicting outcomes of shockwave lithotripsy, ureteroscopy, and spontaneous stone passage. METHODS: We performed a retrospective, case-control study comparing patients who had successful retrograde stent (SRS) insertions with those who failed stent placement and ultimately required nephrostomy tube (NT) insertion (2013-2019). Patients were identified using administrative data from a shared electronic medical record (capturing all urology patients in our geographic area) and a prospective database capturing all institutional interventional radiology procedures. Patient demographics, as well as clinical and stone characteristics were then collected, and imaging manually reviewed. Statistical analysis was performed using univariate and multivariate logistic regression analysis in collaboration with a statistician. RESULTS: A total of 109 patients met inclusion for analysis (34 FRS, 75 SRS). The most common indication for stent insertion included sepsis (79%). On multivariate analysis both acute kidney injury as primary indication for stent insertion (odds ratio [OR] 9.16, 95% confidence interval [CI] 1.91-44.00, p=0.006) and UWT (OR 0.34, 95% CI 0.15-0.74, p=0.007) were found to be significantly associated with failed retrograde stent placement. A receiver operator characteristic curve analysis demonstrates an optimal UWT cutoff of 3.2 mm (sensitivity 60.6%, specificity 83.3%). CONCLUSIONS: Elevated UWT and acute kidney injury as an indication for urgent urinary decompression in the setting of obstructing ureteric stones are predictive of failed retrograde stent placement. These patients may benefit from upfront nephrostomy tube insertion.

Designing a mobile phone-based intervention to promote adherence to antiretroviral therapy in South India.

Integration of mobile phone technology into HIV care holds potential, particularly in resource-constrained settings. Clinic attendees in urban and rural South India were surveyed to ascertain usage of mobile phones and perceptions of their use as an adherence aid. Mobile phone ownership was high at 73%; 26% reported shared ownership. A high proportion (66%) reported using phones to call their healthcare provider. There was interest in weekly telephonic automated voice reminders to facilitate adherence. Loss of privacy was not considered a deterrent. The study presents important considerations in the design of a mobile phone-based adherence intervention in India.

Direct to cystoscopy: A prospective quality assessment of patient preferences.

INTRODUCTION: Cystourethroscopy is one of the most common procedures performed by urologists in both office and operative settings. With the recent centralization of cystoscopy at our center, we looked to assess our current delivery model, to determine whether patients prefer their initial visit to be in cystoscopy or in the clinic, followed by a cystoscopy appointment later. METHODS: We administered 500 prospective questionnaires to adults undergoing cystoscopy by 14 urologists at our center in 2017. Patient demographics were collected, along with their questionnaire results that we compared to their urologist-reported indication, results, and plan. Our primary objective was to assess whether patients prefer to be seen direct to cystoscopy (DTC) vs. a clinic appointment (CA) before cystoscopy. RESULTS: A total of 500 questionnaires were analyzed, with 336/500 (67%) patients being male. Mean age was 66 years (21-93), with 30% under 60 years. Thirty-nine percent (n=193) were undergoing their first cystoscopy, with 85% preferring DTC. There was no difference in age, gender, first-time cystoscopy, or indication for cystoscopy when comparing those who preferred DTC vs. CA. Patients who had an accurate understanding of the indication for their cystoscopy had 6.23 times higher odds of preferring DTC (p<0.05). We also identified a deficiency in patient comprehension of cystoscopy results and followup plans. CONCLUSIONS: With limited health resources, a large patient catchment area, and the majority of patients preferring to be seen DTC, there is evidence to implement a default DTC approach to booking cystoscopy clinics.

Impact of LUTS on urine volume in stone formers The impact of lower urinary tract symptomatology on urine volumes in stone formers.

INTRODUCTION: We aimed to determine if there is a correlation between International Prostate Symptom scores (IPSS) and 24-hour urine collection volumes, as patients experiencing lower urinary tract symptoms (LUTS) may have impaired ability to increase fluid intake for stone prevention. METHODS: We conducted a single-centre, retrospective review was performed of stone-formers presenting from 2014-2016. Inclusion criteria were completion of an IPSS questionnaire and a 24-hour urine collection. Exclusion criteria included symptomatic stone or urinary tract infection at time of IPSS completion, inadequate 24-hour collection, or incomplete IPSS questionnaire. RESULTS: A total of 131 patients met inclusion criteria. Stratification by IPSS severity into mild (0-7), moderate (8-19), and severe (20-35) yielded groups of n=96, 28, and 7, respectively. Linear regression modelling did not reveal a correlation between IPSS score and volume (p=0.10). When compared to those with adequate urine volumes (>2 L/day, n=65), low-volume patients (<1 L/day, n=10) had a significantly higher total IPSS (11.7 vs. 6.1; p=0.036). These groups showed significant differences in their responses to questions about incomplete emptying (p=0.031), intermittency (p=0.011), and stranguria (p=0.0020), with higher scores noted in the low urine output group. CONCLUSIONS: This study is the first to examine the correlation between IPSS and 24-hour urine volume. Though our data does not show a linear relationship between urine output and IPSS, those with lower urine volumes appear to have worse self-reported voiding symptoms when compared to those with adequate volumes (>2 L/day) for stone prevention. The overall number of patients in our study is relatively small, which may account for the lack of a relationship between IPSS and 24-hour urine volumes.

Are We Banging Our Heads Against the Wall? The Effect of Treatment Head Wear on the Outcomes of Extracorporeal Shockwave Lithotripsy.

INTRODUCTION AND OBJECTIVE: The manufacturer for the Storz Modulith SLX-F2 lithotripter recommends treatment head exchange after 1.65 million shocks. However, there is no documentation describing longevity of the treatment head with continued usage. The objective of this study is to determine whether there is a difference in stone fragmentation effectiveness with the treatment head at the beginning versus the end of its treatment life. METHODS: We conducted a retrospective chart review of 200 patients-50 consecutive patients treated immediately preceding, and following, two separate treatment head exchanges. Primary outcome measures were stone-free rate (no stone), total stone fragmentation (any decrease in size), and fragmentation rate ≤4 mm (decrease in size with largest residual fragment ≤4 mm), based on most recent follow-up imaging post shockwave. RESULTS: There were no baseline characteristic differences between the pre-exchange and postexchange groups with respect to first time lithotripsy for the stone (85% vs. 77%), stone location, preoperative stenting (3% vs. 4%), mean stone density (912 hounsfield units [HU] vs. 840 HU), mean stone size (9.0 mm vs. 8.1 mm), stone location, and mean number of shocks delivered (3105 vs. 3089). Mean time to follow-up was 2.7 weeks in both groups, with most follow-up imaging consisting of a kidney ureter bladder X-ray (87% pre-exchange vs. 85% postexchange). Stone free (34% vs. 27%), total stone fragmentation (76% vs. 76%), fragmentation ≤4 mm (48% vs. 42%), re-treatment rates (38% vs. 51%), and complication rates (6% vs. 7%), were not statistically different between the pre and postexchange groups, respectively. CONCLUSIONS: Exchanging the Storz Modulith F2 lithotripter head at the manufacturer recommended 1.65 million shocks does not affect the stone-free or fragmentation rate. If the manufacturer's recommendation for treatment head longevity is based on clinical outcomes, then there is likely room to extend this number without affecting treatment efficacy.

Principles and Practices Fostering Inclusive Excellence: Lessons from the Howard Hughes Medical Institute's Capstone Institutions.

Best-practices pedagogy in science, technology, engineering, and mathematics (STEM) aims for inclusive excellence that fosters student persistence. This paper describes principles of inclusivity across 11 primarily undergraduate institutions designated as Capstone Awardees in Howard Hughes Medical Institute's (HHMI) 2012 competition. The Capstones represent a range of institutional missions, student profiles, and geographical locations. Each successfully directed activities toward persistence of STEM students, especially those from traditionally underrepresented groups, through a set of common elements: mentoring programs to build community; research experiences to strengthen scientific skill/identity; attention to quantitative skills; and outreach/bridge programs to broaden the student pool. This paper grounds these program elements in learning theory, emphasizing their essential principles with examples of how they were implemented within institutional contexts. We also describe common assessment approaches that in many cases informed programming and created traction for stakeholder buy-in. The lessons learned from our shared experiences in pursuit of inclusive excellence, including the resources housed on our companion website, can inform others' efforts to increase access to and persistence in STEM in higher education.

The effect of different light regimes on adult life span in Drosophila melanogaster is partly mediated through reproductive output.

The effects of different light regimes on the fitness of organisms have typically been studied using mean or median adult life span as the sole index of physiological well-being. It is, however, known that life span is inversely related to reproductive output in many species. Moreover, the effects of a given environmental treatment on life span can be due to effects on either age-independent mortality or the "rate of aging," or a combination of both. Drawing evolutionary inferences from the effects of light regime on mean or median adult life span alone is difficult and, at best, speculative. We examined the effects of constant light (LL), alternating light-dark cycles (LD 12:12 h), and constant darkness (DD) on the life span of reproducing and virgin flies in four populations of Drosophila melanogaster and also estimated lifetime fecundity in the three light regimes. The light regime effects on life span were further dissected by examining the age-independent mortality and the Gompertz rate of aging under the three light regimes. While mean adult life span of reproducing males and females and virgin females was significantly shorter in LL compared to LD 12:12 h and DD, life-time egg production was highest in LL. Life span of virgin males was not significantly affected by light regime. The rate of aging in reproducing females was higher in LL as compared to DD, whereas age-independent mortality was higher in DD. As reproductive output, especially early in life, is a far more significant contributor to fitness than is life span, our results suggest that the earlier reported deleterious effects of LL on fitness are partly an artifact of examining life span alone, without considering other components of adult fitness that trade off with life span. Our results suggest that detailed investigation of the effects of light regime on the physiological and behavioral processes that accompany reproduction is necessary to fully understand the effects of different light regimes on adult fitness in Drosophila.

Immobilization of heavy metals from aqueous solutions using polyacrylamide grafted hydrous tin (IV) oxide gel having carboxylate functional groups.

A new adsorbent containing a carboxylate group has been prepared by the surface modification of a polyacrylamide grafted hydrous tin (IV) oxide gel. The product exhibits a very high adsorption potential for Pb(II), Hg(II) and Cd(II). The effect of initial metal ion concentration, adsorbent dose, pH, concentration of light metal ions, and temperature on metal removal has been studied. The process follows a first-order rate kinetics. The intraparticle diffusion of metal ions through pores in the adsorbent was shown to be the main rate limiting step. The equilibrium data fit well with the Langmuir adsorption isotherm. The selectivity order of the adsorbent is Pb(II) > Hg(II) > Cd(II). Adsorption rate constants and thermodynamic parameters were also presented to predict the nature of adsorption. The method was applied on synthetic wastewaters. Acid regeneration has been tried for several cycles with a view to recover the adsorbed metal ions and also to restore the sorbent to its original state.

Changing trends in the American diet and the rising prevalence of kidney stones.

OBJECTIVE: To evaluate the trends in the American diet over the last 40 years (1974-2010), during which time the National Health and Nutrition Examination Survey data set has documented an increase in stone prevalence from 3.8% to 8.8%. MATERIALS AND METHODS: We used the National Health and Nutrition Examination Survey reported rates for stone disease (1974-2010) to compare the United States Department of Agriculture's food distribution data during the same period. Three data points for prevalence were used from the literature. We correlated these to changing lithogenic food distributions using linear models to interpolate annual changes in prevalence. Spearman correlations were performed (P ≤.05) using SAS 9.2 (SAS Institute, Cary, NC). RESULTS: Increased total daily calories (rho, 0.96; P <.001), fat (rho, 0.79; P <.001), protein (rho, 0.85; P <.001), fruit (rho, 0.6; P = .01), and vegetables (rho, 0.73; P <.001) correlated strongly with increasing stone prevalence. Dark green vegetables, flour or cereal products, fish or shellfish, corn products (including high fructose corn syrup), and added sugars also showed strong correlations with stone prevalence. Citrus fruits were negatively correlated to stone disease (rho, -0.18; P = .31). Protein, fruits and vegetables, and added sugars actually decreased in proportion to daily caloric per capita increases. CONCLUSION: Increases in caloric intake and several lithogenic foods correlate temporally with increasing stone prevalence. The nature of this relationship is difficult to determine from this data; although, clearly, American diets have changed over the last 4 decades.

Simultaneous inhibition of cell-cycle, proliferation, survival, metastatic pathways and induction of apoptosis in breast cancer cells by a phytochemical super-cocktail: genes that underpin its mode of action.

Traditional chemotherapy and radiotherapy for cancer treatment face serious challenges such as drug resistance and toxic side effects. Complementary / Alternative medicine is increasingly being practiced worldwide due to its safety beneficial therapeutic effects. We hypothesized that a super combination (SC) of known phytochemicals used at bioavailable levels could induce 100% killing of breast cancer (BC) cells without toxic effects on normal cells and that microarray analysis would identify potential genes for targeted therapy of BC. Mesenchymal Stems cells (MSC, control) and two BC cell lines were treated with six well established pro-apoptotic phytochemicals individually and in combination (super cocktail), at bioavailable levels. The compounds were ineffective individually. In combination, they significantly suppressed BC cell proliferation (>80%), inhibited migration and invasion, caused cell cycle arrest and induced apoptosis resulting in 100% cell death. However, there were no deleterious effects on MSC cells used as control. Furthermore, the SC down-regulated the expression of PCNA, Rb, CDK4, BcL-2, SVV, and CD44 (metastasis inducing stem cell factor) in the BC cell lines. Microarray analysis revealed several differentially expressed key genes (PCNA, Rb, CDK4, Bcl-2, SVV, P53 and CD44) underpinning SC-promoted BC cell death and motility. Four unique genes were highly up-regulated (ARC, GADD45B, MYLIP and CDKN1C). This investigation indicates the potential for development of a highly effective phytochemical combination for breast cancer chemoprevention / chemotherapy. The novel over-expressed genes hold the potential for development as markers to follow efficacy of therapy.

High-glucose-induced endothelial cell injury is inhibited by a Peptide derived from human apolipoprotein E.

Although the importance of human apolipoprotein E (apoE) in vascular diseases has clearly been established, most of the research on apoE has focused on its role in cholesterol metabolism. In view of the observation that apoE and its functional domains impact extracellular matrix (ECM) remodeling, we hypothesized that apoE could also confer protection against ECM degradation by mechanisms independent of its role in cholesterol and lipoprotein transport. The ECM degrading enzyme, heparanase, is secreted by cells as pro-heparanase that is internalized through low-density lipoprotein (LDL) receptor-related protein-1 (LRP-1) to become enzymatically active. Both apoE and pro-heparanase bind the LRP-1. We further hypothesized that an apoE mimetic peptide (apoEdp) would inhibit the production of active heparanase by blocking LRP-1-mediated uptake of pro-heparanase and thereby decrease degradation of the ECM. To test this hypothesis, we induced the expression of heparanase by incubating human retinal endothelial cells (hRECs) with high glucose (30 mM) for 72 hours. We found that elevated expression of heparanase by high glucose was associated with increased shedding of heparan sulfate (ΔHS) and the tight junction protein occludin. Treatment of hRECs with 100 µM apoEdp in the presence of high glucose significantly reduced the expression of heparanase, shedding of ΔHS, and loss of occludin as detected by Western blot analysis. Either eye drop treatment of 1% apoEdp topically 4 times a day for 14 consecutive days or intraperitoneal injection (40 mg/kg) of apoEdp daily for 14 consecutive days in an in vivo mouse model of streptozotocin-induced diabetes inhibited the loss of tight junction proteins occludin and zona occludin- 1 (ZO-1). These findings imply a functional relationship between apoE and endothelial cell matrix because the deregulation of these molecules can be inhibited by a short peptide derived from the receptor-binding region of apoE. Thus, strategies targeting ECM-degrading enzymes could be therapeutically beneficial for treating diabetic retinopathy.

Salvage hypospadias repairs.

AIM: Review of our experience and to develop an algorithm for salvage procedures in the management of hypospadias cripples and treatment of urethral strictures following hypospadias repair. METHODS: This is a retrospective review of hypospadias surgeries over a 41-month period. Out of a total 168 surgeries, 20 were salvage/re-operative repairs. In three children a Duplay repair was feasible, while in four others a variety of single-stage repairs could be done. The repair was staged in seven children - buccal mucosal grafts (BMGs) in five, buccal mucosal tube in one, and skin graft in one. Five children with dense strictures were managed by dorsal BMG inlay grafting in one, vascularized tunical onlay grafting on the ventrum in one, and a free tunical patch in one. Three children were treated by internal urethrotomy and stenting for four weeks with a poor outcome. RESULTS: The age of children ranged from 1.5-15 years (mean 4.5). Follow-up ranged from 3 months to 3.5 years. Excellent results were obtained in 10 children (50%) with a well-surfaced erect penis and a slit-like meatus. Glans closure could not be achieved and meatus was coronal in three. Two children developed fistulae following a Duplay repair and following a staged BMG. Three repairs failed completely - a composite repair broke down, a BMG tube stenosed with a proximal leak, and a stricture recurred with loss of a ventral free tunical graft. CONCLUSIONS: In salvage procedures performed on hypospadias cripples, a staged repair with buccal mucosa as an inlay in the first stage followed by tubularization 4-6 months later provides good results. A simple algorithm to plan corrective surgery in failed hypospadias cases and obtain satisfactory results is devised.