Differentiation of renal masses with multi-parametric MRI: the de Silva St George classification scheme.

PURPOSE: To develop a system for multi-parametric MRI to differentiate benign from malignant solid renal masses and assess its accuracy compared to the gold standard of histopathological diagnosis. METHODS: This is a retrospective analysis of patients who underwent 3 Tesla mpMRI for further assessment of small renal tumours with specific scanning and reporting protocol incorporating T2 HASTE signal intensity, contrast enhancement ratios, apparent diffusion coefficient and presence of microscopic/macroscopic fat. All MRIs were reported prior to comparison with histopathologic diagnosis and a reporting scheme was developed. 2 × 2 contingency table analysis (sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV)), Fisher Exact test were used to assess the association between suspicion of malignancy on mpMRI and histopathology, and descriptive statistics were performed. RESULTS: 67 patients were included over a 5-year period with a total of 75 renal masses. 70 masses were confirmed on histopathology (five had pathognomonic findings for angiomyolipomas; biopsy was therefore considered unethical, so these were included without histopathology). Three patients were excluded due to a non-diagnostic result, non-standardised imaging and one found to be an organising haematoma rather than a mass. Therefore 72 cases were included in analysis (in 64 patients, with seven patients having multiple tumours). Unless otherwise specified, all further statistics refer to individual tumours rather than patients. 52 (72.2%) were deemed 'suspicious or malignant' and 20 (27.8%) were deemed 'benign' on mpMRI. 51 cases (70.8%) had renal cell carcinoma confirmed. The sensitivity, NPV, specificity and PPV for MRI for detecting malignancy were 96.1%, 90%, 85.7% and 94.2% respectively, Fisher's exact test demonstrated p < 0.0001 for the association between suspicion of malignancy on MRI and histopathology. CONCLUSION: The de Silva St George classification scheme performed well in differentiating benign from malignant solid renal masses, and may be useful in predicting the likelihood of malignancy to determine the need for biopsy/excision. Further validation is required before this reporting system can  be recommended for clinical use.

Antibody-Oligonucleotide Conjugation Using a SPAAC Copper-Free Method Compatible with 10× Genomics' Single-Cell RNA-Seq.

Recent advances in multimodal approaches toward single-cell analyses present valuable data points that can complement standard flow cytometry data. In particular, the overlay of cell-surface proteome data with gene expression analysis presents a necessary advancement, particularly in the field of immunology. Here we describe a copper-free click chemistry method for the generation of antibody-oligonucleotide complexes and present the steps for its employment in the context of the 10× genomics droplet-based single-cell RNA-seq workflow, providing a method for coupling proteomic and transcriptomic analyses in an efficient and cost-effect manner.

Genetic variation influencing DNA methylation provides insights into molecular mechanisms regulating genomic function.

We determined the relationships between DNA sequence variation and DNA methylation using blood samples from 3,799 Europeans and 3,195 South Asians. We identify 11,165,559 SNP-CpG associations (methylation quantitative trait loci (meQTL), P < 10-14), including 467,915 meQTL that operate in trans. The meQTL are enriched for functionally relevant characteristics, including shared chromatin state, High-throuhgput chromosome conformation interaction, and association with gene expression, metabolic variation and clinical traits. We use molecular interaction and colocalization analyses to identify multiple nuclear regulatory pathways linking meQTL loci to phenotypic variation, including UBASH3B (body mass index), NFKBIE (rheumatoid arthritis), MGA (blood pressure) and COMMD7 (white cell counts). For rs6511961 , chromatin immunoprecipitation followed by sequencing (ChIP-seq) validates zinc finger protein (ZNF)333 as the likely trans acting effector protein. Finally, we used interaction analyses to identify population- and lineage-specific meQTL, including rs174548 in FADS1, with the strongest effect in CD8+ T cells, thus linking fatty acid metabolism with immune dysregulation and asthma. Our study advances understanding of the potential pathways linking genetic variation to human phenotype.

Very long-term follow-up of autologous pubovaginal fascia slings in women with stress urinary incontinence.

INTRODUCTION AND HYPOTHESIS: The objective was to report on the very long-term outcome of a published series of autologous pubovaginal slings (PVS) in women with stress urinary incontinence (SUI). METHODS: Following institutional review board approval, a cohort of well characterized, non-neurogenic women who underwent an autologous PVS (primary [PVS1] and secondary [PVS2]) for SUI was re-evaluated for their very long-term outcome status. Data collected included demographics, validated questionnaires (Urogenital Distress Inventory - short form [UDI-6], Incontinence Impact Questionnaire - short form 7, quality of life), SUI retreatment/operations, and subjective patient-reported SUI improvement (%) and symptom recurrence. The primary outcome was success defined as UDI-6 question 3 (SUI) ≤ 1 and no SUI retreatment/operation. Patients not seen in clinic for 2 years were contacted via a standardized phone interview. RESULTS: From 83 patients with 7-year intermediate follow-up data, 34 (PVS1 = 18, PVS2 = 16) had very long-term follow-up based on clinic visit (7) or phone interviews (27). Those lost to follow-up (49), including 5 deceased, did not differ in demographics and intermediate outcomes from the followed cohort, but lived further away (>75 miles). At a mean age of 74 years, and with a median follow-up of 14.5 years, 53% met the success criteria (PVS1 = 44%, PVS2 = 63%). Mean postoperative questionnaire scores did not differ significantly between intermediate and very long-term follow-ups, and long-term outcomes between PVS1 and PVS2 remained similar. CONCLUSIONS: A majority of women with long-term follow-up after PVS for primary and secondary SUI remained successful more than 14 years after their surgery. Both groups, PVS1 and PVS2, fared equally well, confirming the durability of PVS as a treatment alternative for SUI.

The diagnostic utility of diffusion weighted MRI imaging and ADC ratio to distinguish benign from malignant renal masses: sorting the kittens from the tigers.

BACKGROUND: MRI is playing an increasing role in risk stratification and non-invasive diagnosis of the undifferentiated small renal mass. This study was designed to assess the reliability of MRI in diagnostic evaluation of renal masses, specifically characterising lesions with diffusion weighted imaging (DWI) and apparent diffusion coefficient (ADC) values. METHODS: This is a retrospective analysis of patients undergoing MRI as part of their clinical workup for a renal mass suspicious for renal cell carcinoma (RCC) on CT or ultrasound followed by biopsy and/or surgical excision. All cases were conducted on 3 Tesla MRI, with conventional breath-held sequences, DWI and dynamic contrast enhanced phases. Tumour regions of interest were evaluated on ADC maps and compared with T2 weighted and post-contrast images. RESULTS: Of the 66 renal tumours included, 33 (50.0%) were Clear Cell RCC, 11 (16.7%) were Oncocytoma, nine (13.6%) were Angiomyolipoma (AML), nine (13.6%) were Papillary RCC and four (6.1%) were Chromophobe RCC. Oncocytoma had the largest ADC values, significantly larger than AMLs and all RCC subtypes (p < 0.001). The average ADC value was also significantly larger in Clear Cell RCCs compared to AMLs, and other RCC subtypes (p < 0.001). CONCLUSIONS: MRI with DWI/ADC imaging may aid the differentiation of oncocytomas from RCCs and stratify RCC subtypes, Further studies are required to validate these findings. TRIAL REGISTRATION: Not applicable/retrospective study.

Chemical shift imaging in the identification of those renal tumours that contain microscopic fat and the utility of multiparametric MRI in their differentiation.

INTRODUCTION: The aim of this study was to assess the qualitative and MRI findings of renal tumours, to determine which lesions contain microscopic fat, one of the potential differentiating factors between tumour types. METHODS: 73 patients who underwent 3 Tesla MRI including chemical shift imaging, with subsequent biopsy or excision for histopathological diagnosis, were included in the study. The images were reviewed for a decrease in signal intensity (SI) on the opposed phase compared with the in-phase gradient echo T1 images, indicating the presence of microscopic fat. The chemical shift index was then calculated as a percentage of SI change and compared with the pathological diagnosis. RESULTS: In total, 38 (52%) of lesions demonstrated a decrease in SI, consistent with microscopic fat. Microscopic fat was found in 28 (80%) clear cell renal cell carcinomas (RCCs), 6 (66.7%) angiomyolipomas, 2 (20%) papillary RCCs, 1 (20%) chromophobe RCC and 1 (9.1%) oncocytoma. Pairwise comparison of means indicated that the amount of microscopic fat was significantly larger only for angiomyolipomas compared with clear cell RCCs (P < 0.001) and other renal lesions (P < 0.001). CONCLUSIONS: A decrease in SI on opposed phase compared with in-phase chemical shift imaging favours the diagnosis of either clear cell RCC or an angiomyolipoma. When combined with other parameters in mpMRI, this may aid differentiation of benign from malignant tumours and differentiation of aggressive from indolent RCC subtypes. This may be of value where biopsy is non-diagnostic, not feasible due to location or in high-risk patients.

Protecting Frontline Health Care Workers from COVID-19 with Hydroxychloroquine Pre-exposure Prophylaxis: A structured summary of a study protocol for a randomised placebo-controlled multisite trial in Toronto, Canada.

OBJECTIVES: Primary Objective: To determine if pre-exposure prophylaxis (PrEP) with 400mg hydroxychloroquine (HCQ), taken orally once daily reduces microbiologically confirmed COVID-19 among front line health care workers at high risk for SARS-CoV-2 exposure. Secondary Objectives: To compare the following between study arms: adverse events; symptomatic COVID-19; duration of symptomatic COVID-19; days hospitalized attributed to COVID-19; respiratory failure attributable to COVID-19 requiring i) non-invasive ventilation or ii) intubation/mechanical ventilation; mortality attributed to COVID-19, number of days unable to work attributed to COVID-19, seroconversion (COVID-19 negative to COVID-19 positive over the study period); ability of participant plasma to neutralize SARS-CoV-2 virus in vitro; To describe short-term psychological distress associated with risk of COVID-19 exposure at 1, 60, 120 days of the study. To explore laboratory markers within participants with confirmed COVID-19: including circulating markers of host immune and endothelial activation in participant plasma and their correlation with disease severity and outcome TRIAL DESIGN: The HEROS study is a two-arm, parallel-group, individually randomized (1:1 allocation ratio), placebo controlled, participant and investigator-blinded, multi-site superiority trial of oral HCQ 400 mg taken once daily for 90 days as PrEP to prevent COVID-19 in health care workers at high risk of SARS-CoV-2 exposure. At 90 days, there is an open label extension wherein all participants are offered a one-month course of HCQ 400mg once daily for PrEP of COVID-19. PARTICIPANTS: Frontline HCWs aged 18 years of age or older, at high risk of SARS-CoV-2 exposure (including staff of emergency departments, intensive care units, intubation teams, COVID-wards, and staff deployed to Long Term Care facilities) of five academic hospitals in downtown Toronto, Canada. Exclusion criteria include: currently pregnant, planning to become pregnant during the study period, and/or breast feeding; known hypersensitivity/allergy to hydroxychloroquine or to 4-aminoquinoline compounds; current use of hydroxychloroquine; known prolonged QT syndrome and/or baseline resting ECG with QTc>450 ms and/or concomitant medications which simultaneously may prolong the QTc that cannot be temporarily suspended/replaced; known pre-existing retinopathy, G6PD deficiency, porphyria, liver disease including cirrhosis, encephalopathy, hepatitis or alcoholism, diabetes on oral hypoglycemics or insulin, or renal insufficiency/failure; disclosure of self-administered use of hydroxychloroquine or chloroquine within 12 weeks prior to study; confirmed symptomatic COVID-19 at time of enrollment. INTERVENTION AND COMPARATOR: Intervention: hydroxychloroquine, 400mg (2 tablets) orally per day. Comparator: placebo, two tablets visually identical to the intervention, orally per day MAIN OUTCOMES: The primary outcome is microbiologically confirmed COVID-19 (i.e. SARS-CoV-2 infection). This is a composite endpoint which includes positive results from any validated SARS-CoV-2 diagnostic assay including detection of viral RNA, and/or seroconversion. Participants will be assessed at baseline, and then undergo monthly follow-up at day 30, 60, and 90, 120. At each visit, participants will provide an oropharyngeal sample, blood sample, and will undergo electrocardiogram monitoring of the QTc interval. Secondary outcome measures include: adverse events; symptom duration of COVID-19; days of hospitalization attributed to COVID-19; respiratory failure requiring ventilator support attributed to COVID-19; mortality attributed to COVID-19; total days off work attributed to COVID-19; seropositivity (reactive serology by day 120); and short term psychological impact of exposure to SARS-CoV-2 at day 1, 60, 120 days using the K10, a validated measure of non-specific psychological distress. RANDOMISATION: Within each site, participants will be individually randomized to either the intervention arm with HCQ or the placebo arm using a fixed 1:1 allocation ratio using an interactive web-based response system to ensure concealment of allocation. Randomization schedules will be computer-generated and blocked using variable block sizes. BLINDING (MASKING): All participants, research coordinators, technicians, clinicians and investigators will be blinded to the participant allocation group. Numbers to be randomised (sample size) N=988, randomised into two groups of 494 patients. TRIAL STATUS: This summary describes protocol version No. 1.6, May 15, 2020. Recruitment is ongoing - started April 20, 2020 and anticipated end date is July 30, 2021 TRIAL REGISTRATION: ISRCTN.com Identifier: ISRCTN14326006, registered April 14, 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).

Management of Pelvic Organ Prolapse After Radical Cystectomy.

PURPOSE OF REVIEW: This article explores the anatomy, management options, and outcomes of pelvic organ prolapse with a female cystectomy patient. RECENT FINDINGS: There is a lack of data on surgical management outcomes for prolapse following radical cystectomy. However, most case series from tertiary referral centers show reasonable results irrespective of route of repair. As expected, the surgical planes and the reorientation of the bowel loop for urinary diversion makes any pelvic reconstruction a potential hazard and requires a high level of expertise and counseling to the patient in regard to the management of expectations. Pelvic organ prolapse following radical cystectomy is uncommon but presents a significant challenge to the reconstructive surgeon.

Rituximab or Cyclosporine in the Treatment of Membranous Nephropathy.

BACKGROUND: B-cell anomalies play a role in the pathogenesis of membranous nephropathy. B-cell depletion with rituximab may therefore be noninferior to treatment with cyclosporine for inducing and maintaining a complete or partial remission of proteinuria in patients with this condition. METHODS: We randomly assigned patients who had membranous nephropathy, proteinuria of at least 5 g per 24 hours, and a quantified creatinine clearance of at least 40 ml per minute per 1.73 m2 of body-surface area and had been receiving angiotensin-system blockade for at least 3 months to receive intravenous rituximab (two infusions, 1000 mg each, administered 14 days apart; repeated at 6 months in case of partial response) or oral cyclosporine (starting at a dose of 3.5 mg per kilogram of body weight per day for 12 months). Patients were followed for 24 months. The primary outcome was a composite of complete or partial remission of proteinuria at 24 months. Laboratory variables and safety were also assessed. RESULTS: A total of 130 patients underwent randomization. At 12 months, 39 of 65 patients (60%) in the rituximab group and 34 of 65 (52%) in the cyclosporine group had a complete or partial remission (risk difference, 8 percentage points; 95% confidence interval [CI], -9 to 25; P = 0.004 for noninferiority). At 24 months, 39 patients (60%) in the rituximab group and 13 (20%) in the cyclosporine group had a complete or partial remission (risk difference, 40 percentage points; 95% CI, 25 to 55; P<0.001 for both noninferiority and superiority). Among patients in remission who tested positive for anti-phospholipase A2 receptor (PLA2R) antibodies, the decline in autoantibodies to anti-PLA2R was faster and of greater magnitude and duration in the rituximab group than in the cyclosporine group. Serious adverse events occurred in 11 patients (17%) in the rituximab group and in 20 (31%) in the cyclosporine group (P = 0.06). CONCLUSIONS: Rituximab was noninferior to cyclosporine in inducing complete or partial remission of proteinuria at 12 months and was superior in maintaining proteinuria remission up to 24 months. (Funded by Genentech and the Fulk Family Foundation; MENTOR ClinicalTrials.gov number, NCT01180036.).

An update on research and outcomes in surgical management of vaginal mesh complications.

INTRODUCTION: Stress urinary incontinence and pelvic organ prolapse are major quality of life conditions affecting millions of individuals. Transvaginal mesh materials have been proposed to supplant native tissue repairs. However, these materials have opened a new field, meshology, devoted to the management of mesh complications. AREAS COVERED: This review highlights some of the recent developments in this subspecialty which often requires a multidisciplinary approach. With better imaging, the preoperative assessment of mesh complications has been enhanced. Specialized centers with high volumes are best suited to handle these challenging patients who fear the many risks of mesh removal and the uncertainties of their clinical status after the removal procedure(s). However, despite a better classification system recommended by specialized societies, the multidimensional outcome of these repair procedures will require the adoption of outcome tools which can cover several domains such as urinary incontinence, pelvic pain, dyspareunia, bladder infections, to name a few. EXPERT OPINION: The surgical approach to mesh removal is also evolving with some experts recommending complete removal while others prefer more selective excision. Finally, the long-term outcome of these mesh removal procedures is not yet fully known.

Robust CTCF-Based Chromatin Architecture Underpins Epigenetic Changes in the Heart Failure Stress-Gene Response.

BACKGROUND: The human genome folds in 3 dimensions to form thousands of chromatin loops inside the nucleus, encasing genes and cis-regulatory elements for accurate gene expression control. Physical tethers of loops are anchored by the DNA-binding protein CTCF and the cohesin ring complex. Because heart failure is characterized by hallmark gene expression changes, it was recently reported that substantial CTCF-related chromatin reorganization underpins the myocardial stress-gene response, paralleled by chromatin domain boundary changes observed in CTCF knockout. METHODS: We undertook an independent and orthogonal analysis of chromatin organization with mouse pressure-overload model of myocardial stress (transverse aortic constriction) and cardiomyocyte-specific knockout of Ctcf. We also downloaded published data sets of similar cardiac mouse models and subjected them to independent reanalysis. RESULTS: We found that the cardiomyocyte chromatin architecture remains broadly stable in transverse aortic constriction hearts, whereas Ctcf knockout resulted in ≈99% abolition of global chromatin loops. Disease gene expression changes correlated instead with differential histone H3K27-acetylation enrichment at their respective proximal and distal interacting genomic enhancers confined within these static chromatin structures. Moreover, coregulated genes were mapped out as interconnected gene sets on the basis of their multigene 3D interactions. CONCLUSIONS: This work reveals a more stable genome-wide chromatin framework than previously described. Myocardial stress-gene transcription responds instead through H3K27-acetylation enhancer enrichment dynamics and gene networks of coregulation. Robust and intact CTCF looping is required for the induction of a rapid and accurate stress response.

Vaginal Approach to Vesicovaginal Fistula.

Vesicovaginal fistula is the most commonly encountered sequela of genitourinary trauma. Although the etiology differs between developed and developing countries, the principles of fistula repair must be strictly adhered to for success. Timing and route of repair remain contentious, because of a lack of randomized data. Evaluation and management is dictated by the surgeon's experience. Minimally invasive techniques with laparoscopy and robotic technology are generating wider interest with reduced postoperative morbidity, but a transvaginal technique should be in the arsenal of all pelvic reconstructive surgeons. More research is required to evaluate the optimal surgical route and technique for successful outcomes.

Transparent superhydrophilic and superhydrophobic nanoparticle textured coatings: comparative study of anti-soiling performance.

The anti-soiling (AS) performance of highly reflective, superhydrophilic (SPH, 0° water contact angle) coated mirrors was characterized and compared with that of superhydrophobic (SP, >165° water contact angle) coated mirrors. A simple one-step nanotextured silica nanoparticle coating on a mirror exhibited SPH properties associated with hydrophilic rough surfaces. Another mirror surface post-functionalized with low-surface-energy ligand molecules displayed SP behavior. Both coated mirrors, with no solar reflectance loss, demonstrated excellent AS performance because the engineered surface roughness reduced the adhesive force of dust particles. The daily degradation in solar reflectance induced by dust accumulation under outdoor field testing demonstrated that the SPH- and SP-coated mirrors, compared with an uncoated mirror, maintained higher solar reflectance, which was associated with the designed self-cleaning behavior and natural cleaning. However, over the long term, dust-moisture cementation-evidenced by organic hard water stains on the mirror-initiated unrecoverable reflectance loss on the SP-coated mirror after 3 months, whereas the SPH-coated mirror maintained higher reflectance for 7.5 months. Considering fabrication costs and maintenance, SPH-coated nanotextured mirrors offer potential benefits for application in solar energy harvesting.

Suicide after hospital contact for psychiatric assessment in Hong Kong: A long-term cohort study.

There are few long-term studies on suicide in psychiatric settings in China. The objective of this study was to evaluate the long term suicide risk and its associated factors after the initial psychiatric assessment. Demographic and clinical data of adult subjects receiving psychiatric assessment between 1996 and 2000 in a district hospital in Hong Kong were retrieved from the hospital computer system. Data were matched with completed suicides before June 30 2015 as recorded by the Coroner's Office. From a total of 4078 subjects identified, there were 152 (3.7%) recorded suicides; one-fifth of suicides occurred within one year, and half within 5 years. Cox regression analysis revealed that the risk of suicide after the initial psychiatric assessment was positively associated with deliberate self-harm (Hazard ratio = 2.1; 95%CI = 1.5-3.0; p < 0.001), and negatively associated with 'no psychiatric disorder' (Hazard ratio = 0.4; 95%CI = 0.2-0.6; p = 0.001). The overall suicide risk for those diagnosed to have a psychiatric disorder was 4.4%; 4.5% for men and 4.3% for women. Deliberate self-harm and having a psychiatric disorder at the time of assessment are significant risk factors of suicide. Appropriate treatment of psychiatric disorders and comprehensive management of deliberate self-harm are important for suicide prevention.

Position statement: a clinical approach to the management of adult non-neurogenic overactive bladder.

INTRODUCTION: Overactive bladder (OAB) is a highly prevalent medical condition that has an adverse impact on various health-related quality-of-life domains, including a significant psychosocial and financial burden. This position statement, formulated by members of the Urological Society of Australia and New Zealand and the UroGynaecological Society of Australasia, summarises the current recommendations for clinical diagnosis and treatment strategies in patients with non-neurogenic OAB, and guides clinicians in the decision-making process for managing the condition using evidence-based medicine. Main recommendations: Diagnosis and initial management should be based on thorough clinical history, examination and basic investigations to exclude underlying treatable causes such as urinary tract infection and urological malignancy. Initial treatment strategies for OAB involve conservative management with behavioural modification and bladder retraining. Second-line management involves medical therapy using anticholinergic or ß3 agonist drugs provided there is adequate assessment of bladder emptying. If medical therapy is unsuccessful, further investigations with urodynamic studies and cystourethroscopy are recommended to guide further treatment. Intravesical botulinum toxin and sacral neuromodulation should be considered in medical refractory OAB. Changes in management as a result of this statement: OAB is a constellation of urinary symptoms and is a chronic condition with a low likelihood of cure; managing patient expectations is essential because OAB is challenging to treat. At present, the exact pathogenesis of OAB remains unclear and it is likely that there are multiple factors involved in this disease complex. Current medical treatment remains far from ideal, although minimally invasive surgery can be effective. Further research into the pathophysiology of this common condition will hopefully guide future developments in disease management.

Complications Following the Insertion of Two Synthetic Mid-urethral Slings and Subsequent Removal.

OBJECTIVE: To determine outcomes after removal of two synthetic mid-urethral slings (MUS) at a tertiary care center. METHODS: Following IRB approval, a retrospective chart review of non-neurogenic, symptomatic women requiring re-operation after ≥2 MUS was performed. Data reviewed by a third party included: demographics, prior anti-incontinence surgery, complications, pelvic/urinary symptoms, subsequent investigations, surgical repair and outcomes (including UDI-6/IIQ-7 questionnaires) at a minimum 6 months follow-up. Cure was defined as being continent, no dyspareunia, and no additional surgical therapy. RESULTS: Between 2007 and 2014, 21 women met the inclusion criteria. Mean age was 57 years (range: 40-82) and mean follow-up was 30.2 months (range: 6-78). The majority of patients presented with one or more symptoms of voiding dysfunction (95%), urinary incontinence (86%), irritative voiding symptoms (62%), dyspareunia (57%), recurrent urinary tract infections (UTIs) (29%), vaginal extrusion (20%) and erosion involving the urinary tract (5%). Patients had a mean of 2 prior anti-incontinence procedures (range 2-3). Over two-thirds had a combination of retropubic and transobturator MUS. Mean number of pre-operative investigations was 3.5 (1-6) including voiding cystourethrogram, cystoscopy and urodynamics. Two patients had complete remission, 14 partial remission, and five failed. Mean postoperative total UDI-6 and IIQ-7 scores at last clinic visit were 10 (range: 0-16/SD 4.1) and 11 (range: 0-28/SD 10.3), respectively. CONCLUSION: The management of women with suboptimal outcomes following two synthetic MUS from transvaginal excision results in modest symptomatic improvement but low permanent complete remission and frequent need for additional therapies.

Introducing a model of pairing based on base pair specific interactions between identical DNA sequences.

At present, there have been suggested two types of physical mechanism that may facilitate preferential pairing between DNA molecules, with identical or similar base pair texts, without separation of base pairs. One mechanism solely relies on base pair specific patterns of helix distortion being the same on the two molecules, discussed extensively in the past. The other mechanism proposes that there are preferential interactions between base pairs of the same composition. We introduce a model, built on this second mechanism, where both thermal stretching and twisting fluctuations are included, as well as the base pair specific helix distortions. Firstly, we consider an approximation for weak pairing interactions, or short molecules. This yields a dependence of the energy on the square root of the molecular length, which could explain recent experimental data. However, analysis suggests that this approximation is no longer valid at large DNA lengths. In a second approximation, for long molecules, we define two adaptation lengths for twisting and stretching, over which the pairing interaction can limit the accumulation of helix disorder. When the pairing interaction is sufficiently strong, both adaptation lengths are finite; however, as we reduce pairing strength, the stretching adaptation length remains finite but the torsional one becomes infinite. This second state persists to arbitrarily weak values of the pairing strength; suggesting that, if the molecules are long enough, the pairing energy scales as length. To probe differences between the two pairing mechanisms, we also construct a model of similar form. However, now, pairing between identical sequences solely relies on the intrinsic helix distortion patterns. Between the two models, we see interesting qualitative differences. We discuss our findings, and suggest new work to distinguish between the two mechanisms.

Adult Onset Nocturnal Enuresis: Identifying Causes, Cofactors and Impact on Quality of Life.

OBJECTIVES: The objectives of the present study were: (i) Evaluate common co-pathologies associated with, and potentially contributing to adult onset Nocturnal enuresis (NE) in a tertiary referral population; and (ii) quantify its impact on QoL with validated questionnaires. METHODS: Following Institutional Review Board approval, patients with adult onset NE were reviewed with history, physical examination, urodynamic studies, questionnaires: Overactive bladder questionnaire short-form (OAB-qSF), Urogenital Distress Inventory (UDI-6), AUA symptom score (AUA-SS) and Patient Global Impression scale (PGIS). RESULTS: Between 2004 and 2016, 45 NE patients (19 male, 26 female) were identified. Twenty-five patients (56%) had an associated diagnosis of neurogenic bladder (NGB). Five (11%) reported no other LUTS or associated conditions. Forty (89%) had at least one of the following contributing factors: sedative use, OAB (bothersome symptoms based on UDI-6), voiding dysfunction (also based on UDI-6 or AUA-SS), abnormal UDS finding, and/or confirmed obstructive sleep apnea (OSA). Overall, 20% had two contributing factors, and 31% each had three and four factors. Among all patients, 76% reported sedative use and of 36 patients with UDS, 75% had abnormal findings. Of the 41 questionnaire respondents, mean AUA-SS among men was 22.5 (range 8-35) and mean UDI-6 score among women was 9.3 (range 2-16). Mean PGI-S score was 3.1 (range 1-4) and mean Health Related Quality of Life (HRQL) subscale, as part of the OAB-q SF was 44 (range 22-78). CONCLUSIONS: Nocturnal enuresis is associated with multiple possible co-factors in all populations with majority reporting use of sedating medications. NE is associated with significant symptom bother and impacts greatly on QoL.