Tunneled Tunica Vaginalis Flap for Recurrent Urethrocutaneous Fistulae

The tubularized incised plate (TIP) hypospadias repair is currently the most widely used urethroplasty technique. The most significant post-TIP complication is urethrocutaneous fistula (UCF) development. Tunneled tunica vaginalis flap (TVF) is a well-described technique for the repair of UCF. We retrospectively reviewed all patients undergoing repeat repair of UCF after TIP repair from 2001 to 2005. Twelve boys underwent TVF repair at our institution for recurrent UCF. Fistulae ranged from distal penile to penoscrotal in location. Median surgical time was 45 minutes and no postoperative complications occurred. After a median follow-up of 32 months (range 16–48 months), no patient has yet had a recurrence of UCF. In conclusion, TVF repair is a successful technique for the treatment of UCF after previous failed repair. TVF is technically simple to perform and should be considered for treating UCF following TIP urethroplasty, particularly in a repeat surgical setting

Myofascial urinary frequency syndrome is a novel syndrome of bothersome lower urinary tract symptoms associated with myofascial pelvic floor dysfunction

This study describes a novel, distinct phenotype of urinary symptoms named myofascial urinary frequency syndrome (MUFS) present in one-third of individuals presenting with urinary frequency. In addition to a characteristic symptom constellation suggestive of myofascial dysfunction, MUFS subjects exhibit persistency : a persistent feeling of needing to urinate regardless of urine volume. On examination, 97% of MUFS patients demonstrated pelvic floor hypertonicity with either global tenderness or myofascial trigger points, and 92% displayed evidence of impaired muscular relaxation, hallmarks of myofascial dysfunction. To confirm this symptom pattern was attributable to the pelvic floor musculature, we confirmed the presence of persistency in 68 patients with pelvic floor myofascial dysfunction established through comprehensive examination and electromyography and corroborated by improvement with pelvic floor myofascial release. These symptoms distinguish subjects with myofascial dysfunction from subjects with OAB, IC/BPS, and asymptomatic controls, confirming MUFS is a distinct LUTS symptom complex

Activation and Involvement of Ral GTPases in Colorectal Cancer

Current approaches to block KRAS oncogene function focus on inhibition of K-Ras downstream effector signaling. We evaluated the anti-tumor activity of selumetinib (AZD6244, ARRY-142886), a potent and selective MEK1/2 inhibitor, on a panel of colorectal carcinoma (CRC) cells and found no inhibition of KRAS mutant CRC cell anchorage-independent growth. While AKT activity was elevated in KRAS mutant cells, and PI3K inhibition did impair the growth of MEK inhibitor-insensitive CRC cell lines, concurrent treatment with selumetinib did not provide additional anti-tumor activity. Therefore, we speculated that inhibition of the Ral guanine exchange factor (RalGEF) effector pathway may be a more effective approach for blocking CRC growth. RalGEFs are activators of the related RalA and RalB small GTPases and we found activation of both in CRC cell lines and patient tumors. Interfering RNA stable suppression of RalA expression reduced CRC tumor cell anchorage-independent growth, but surprisingly, stable suppression of RalB greatly enhanced soft agar colony size and formation frequency. Despite their opposing activities, both RalA and RalB regulation of anchorage-independent growth required interaction with RalBP1/RLIP76 and components of the exocyst complex. Interestingly, RalA interaction with the Exo84 but not Sec5 exocyst component was necessary for supporting anchorage-independent growth, whereas RalB interaction with Sec5 but not Exo84 was necessary for inhibition of anchorage-independent growth. We suggest that anti-RalA-selective therapies may provide an effective approach for KRAS mutant CRC

Rare variants in tenascin genes in a cohort of children with primary vesicoureteric reflux

Primary vesicoureteral reflux (PVUR) is the most common malformation of the kidney and urinary tract and reflux nephropathy is a major cause of chronic kidney disease in children. Recently, we reported mutations in tenascin XB (TNXB) as a cause of PVUR with joint hypermobility

Towards a neutron and X-ray reflectometry environment for the study of solid–liquid interfaces under shear

Funder: Infineum UK LtdAbstract: A novel neutron and X-ray reflectometry sample environment is presented for the study of surface-active molecules at solid–liquid interfaces under shear. Neutron reflectometry was successfully used to characterise the iron oxide–dodecane interface at a shear rate of 7.0×102s-1 using a combination of conventional reflectometry theory coupled with the summation of reflected intensities to describe reflectivity from thicker films. Additionally, the structure adopted by glycerol monooleate (GMO), an Organic Friction Modifier, when adsorbed at the iron oxide–dodecane interface at a shear rate of 7.0×102s-1 was studied. It was found that GMO forms a surface layer that appears unaltered by the effect of shear, where the thickness of the GMO layer was found to be 24.3-10.2+9.9 Å under direct shear at 7.0×102s-1 and 25.8-5.2+4.4 Å when not directly under shear. Finally, a model to analyse X-ray reflectometry data collected with the sample environment is also described and applied to data collected at 3.0×103s-1

A Six-Gene Signature Predicts Survival of Patients with Localized Pancreatic Ductal Adenocarcinoma

Jen Jen Yeh and colleagues developed and validated a six-gene signature in patients with pancreatic ductal adenocarcinoma that may be used to better stage the disease in these patients and assist in treatment decisions

A survey and panel discussion of the effects of the COVID-19 pandemic on paediatric urological productivity, guideline adherence and provider stress

Introduction The COVID-19 pandemic has led to an unprecedented need to re-organise and re-align priorities for all surgical specialties. Despite the current declining numbers globally, the direct effects of the pandemic on institutional practices and on personal stress and coping mechanisms remains unknown. The aims of this study were to assess the effect of the pandemic on daily scheduling and work balances, its effects on stress, and to determine compliance with guidelines and to assess whether quarantining has led to other areas of increased productivity. Methods A trans-Atlantic convenience sample of paediatric urologists was created in which panellists (Zoom) discussed the direct effects of the COVID-19 pandemic on individual units, as well as creating a questionnaire using a mini-Delphi method to provide current semi-quantitative data regarding practice, and adherence levels to recently published risk stratification guidelines. They also filled out a Perceived Stress Scale (PSS) questionnaire to assess contemporary pandemic stress levels. Results There was an 86% response rate from paediatric urologists. The majority of respondents reported near complete disruption to planned operations (70%), and trainee education (70%). They were also worried about the effects of altered home-lives on productivity (<= 90%), as well as a lack of personal protective equipment (57%). The baseline stress rate was measured at a very high level (PSS) during the pandemic. Adherence to recent operative guidelines for urgent cases was 100%. Conclusion This study represents a panel discussion of a number of practical implications for paediatric urologists, and is one of the few papers to assess more pragmatic effects and combines opinions from both sides of the Atlantic. The impact of the pandemic has been very significant for paediatric urologists and includes a decrease in the number of patients seen and operated on, decreased salary, increased self-reported stress levels, substantially increased telemedicine usage, increased free time for various activities, and good compliance with guidelines and hospital management decisions

Integrated global assessment of the natural forest carbon potential

Forests are a substantial terrestrial carbon sink, but anthropogenic changes in land use and climate have considerably reduced the scale of this system 1. Remote-sensing estimates to quantify carbon losses from global forests 2–5 are characterized by considerable uncertainty and we lack a comprehensive ground-sourced evaluation to benchmark these estimates. Here we combine several ground-sourced 6 and satellite-derived approaches 2,7,8 to evaluate the scale of the global forest carbon potential outside agricultural and urban lands. Despite regional variation, the predictions demonstrated remarkable consistency at a global scale, with only a 12% difference between the ground-sourced and satellite-derived estimates. At present, global forest carbon storage is markedly under the natural potential, with a total deficit of 226 Gt (model range = 151–363 Gt) in areas with low human footprint. Most (61%, 139 Gt C) of this potential is in areas with existing forests, in which ecosystem protection can allow forests to recover to maturity. The remaining 39% (87 Gt C) of potential lies in regions in which forests have been removed or fragmented. Although forests cannot be a substitute for emissions reductions, our results support the idea 2,3,9 that the conservation, restoration and sustainable management of diverse forests offer valuable contributions to meeting global climate and biodiversity targets