Transurethral En Bloc Resection Versus Standard Resection of Bladder Tumour: A Randomised, Multicentre, Phase 3 Trial.

BACKGROUND: Conventionally, standard resection (SR) is performed by resecting the bladder tumour in a piecemeal manner. En bloc resection of the bladder tumour (ERBT) has been proposed as an alternative technique in treating non-muscle-invasive bladder cancer (NMIBC). OBJECTIVE: To investigate whether ERBT could improve the 1-yr recurrence rate of NMIBC, as compared with SR. DESIGN, SETTING, AND PARTICIPANTS: A multicentre, randomised, phase 3 trial was conducted in Hong Kong. Adults with bladder tumour(s) of ≤3 cm were enrolled from April 2017 to December 2020, and followed up until 1 yr after surgery. INTERVENTION: Patients were randomly assigned to receive either ERBT or SR in a 1:1 ratio. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was 1-yr recurrence rate. A modified intention-to-treat analysis on patients with histologically confirmed NMIBC was performed. The main secondary outcomes included detrusor muscle sampling rate, operative time, hospital stay, 30-d complications, any residual or upstaging of disease upon second-look transurethral resection, and 1-yr progression rate. RESULTS AND LIMITATIONS: A total of 350 patients underwent randomisation, and 276 patients were histologically confirmed to have NMIBC. At 1 yr, 31 patients in the ERBT group and 46 in the SR group developed recurrence; the Kaplan-Meier estimate of 1-yr recurrence rates were 29% (95% confidence interval, 18-37) in the ERBT group and 38% (95% confidence interval, 28-46) in the SR group (p = 0.007). Upon a subgroup analysis, patients with 1-3 cm tumour, single tumour, Ta disease, or intermediate-risk NMIBC had a significant benefit from ERBT. None of the patients in the ERBT group and three patients in the SR group developed progression to muscle-invasive bladder cancer; the Kaplan-Meier estimates of 1-yr progression rates were 0% in the ERBT group and 2.6% (95% confidence interval, 0-5.5) in the SR group (p = 0.065). The median operative time was 28 min (interquartile range, 20-45) in the ERBT group and 22 min (interquartile range, 15-30) in the SR group (p < 0.001). All other secondary outcomes were similar in the two groups. CONCLUSIONS: In patients with NMIBC of ≤3 cm, ERBT resulted in a significant reduction in the 1-yr recurrence rate when compared with SR (funded by GRF/ECS, RGC, reference no.: 24116518; ClinicalTrials.gov number, NCT02993211). PATIENT SUMMARY: Conventionally, non-muscle-invasive bladder cancer is treated by resecting the bladder tumour in a piecemeal manner. In this study, we found that en bloc resection, that is, removal of the bladder tumour in one piece, could reduce the 1-yr recurrence rate of non-muscle-invasive bladder cancer.

Interspecific variation in the diet of Symphalangussyndactylus and Macacanemestrina at Genting Highlands, Pahang, Peninsular Malaysia.

Primate communities in the Genting Highlands consist of a single species of Hylobatidae and four species of Cercopithecidae, which are known to exhibit social interaction behaviour. Thus, a study on the diets of Symphalangussyndactylus (siamang; family Hylobatidae) and Macacanemestrina (pig-tailed macaque; family Cercopithecidae) was carried out at Genting Highlands, in order to compare the dietary preferences and interspecific competition between the two primate families. A DNA metabarcoding approach was used to analyse diet intake using non-invasive samples based on the trnL region. Based on the 140 amplicon sequence variants (ASVs) generated, 26 plant orders, 46 different families, 60 genera and 49 species were identified from 23 different plant classes. Fabaceae and Moraceae were classified as the most preferred plants at the family level for S.syndactylus; meanwhile, Piperaceae and Arecaceae were classified as the most preferred for M.nemestrina. Only six out of the 60 different plant genera classified in this study, were found to be consumed by both species. Therefore, the low similarity of preferred plants in the diets between the two families suggests that there is little interspecific competition. These findings are important for future conservation management of highland primates, especially in the Genting Highlands.

Long-Term Outcomes of Orthotopic Neobladder Versus Ileal Conduit Urinary Diversion in Robot-Assisted Radical Cystectomy (RARC): Multicenter Results from the Asian RARC Consortium.

PURPOSE: Robot-assisted radical cystectomy (RARC) has gained traction in the management of muscle invasive bladder cancer. Urinary diversion for RARC was achieved with orthotopic neobladder and ileal conduit. Evidence on the optimal method of urinary diversion was limited. Long-term outcomes were not reported before. This study was designed to compare the perioperative and oncological outcomes of ileal conduit versus orthotopic neobladder cases of nonmetastatic bladder cancer treated with RARC. PATIENTS AND METHODS: The Asian RARC consortium was a multicenter registry involving nine Asian centers. Consecutive patients receiving RARC were included. Cases were divided into the ileal conduit and neobladder groups. Background characteristics, operative details, perioperative outcomes, recurrence information, and survival outcomes were reviewed and compared. Primary outcomes include disease-free and overall survival. Secondary outcomes were perioperative results. Multivariate regression analyses were performed. RESULTS: From 2007 to 2020, 521 patients who underwent radical cystectomy were analyzed. Overall, 314 (60.3%) had ileal conduit and 207 (39.7%) had neobladder. The use of neobladder was found to be protective in terms of disease-free survival [Hazard ratio (HR) = 0.870, p = 0.037] and overall survival (HR = 0.670, p = 0.044) compared with ileal conduit. The difference became statistically nonsignificant after being adjusted in multivariate cox-regression analysis. Moreover, neobladder reconstruction was not associated with increased blood loss, nor additional risk of major complications. CONCLUSIONS: Orthotopic neobladder urinary diversion is not inferior to ileal conduit in terms of perioperative safety profile and long-term oncological outcomes. Further prospective studies are warranted for further investigation.

Molecular phylogeny confirms the subspecies delineation of the Malayan Siamang (Symphalangussyndactyluscontinentis) and the Sumatran Siamang (Symphalangussyndactylussyndactylus) based on the hypervariable region of mitochondrial DNA.

Siamangs (Symphalangussyndactylus) are native to Peninsular Malaysia, Sumatra and southern Thailand and their taxonomical classification at subspecies level remains unclear. Morphologically, two subspecies were proposed as early as 1908 by Thomas namely Symphalangus s.syndactylus and Symphalanguss.continentis. Thus, this study aims to clarify the Siamang subspecies status, based on mtDNA D-loop sequences. Faecal samples were collected from wild Siamang populations at different localities in Peninsular Malaysia. A 600-bp sequence of the mitochondrial D-loop region was amplified from faecal DNA extracts and analysed along with GenBank sequences representing Symphalangus sp., Nomascus sp., Hylobates sp., Hoolock sp. and outgroups (Pongopygmaeus, Macacafascicularis and Papiopapio). The molecular phylogenetic analysis in this study revealed two distinct clades formed by S.s.syndactylus and S.s.continentis which supports the previous morphological delineation of the existence of two subspecies. Biogeographical analysis indicated that the Sumatran population lineage was split from the Peninsular Malaysian population lineage and a diversification occurrred in the Pliocene era (~ 3.12 MYA) through southward expansion. This postulation was supported by the molecular clock, which illustrated that the Peninsular Malaysian population (~ 1.92 MYA) diverged earlier than the Sumatran population (~ 1.85 MYA). This is the first study to use a molecular approach to validate the subspecies statuses of S.s.syndactylus and S.s.continentis. This finding will be useful for conservation management, for example, during Siamang translocation and investigations into illegal pet trade and forensics involving Malayan and Sumatran Siamangs.

Copolymers of Gelatin-graft-poly(3-hexylthiophene) for Transient Electronics.

As transient electronics continue to advance, the demand for new materials has given rise to the exploration of conducting polymer (CP)-based electronic materials. The big challenge lies in balancing conductivity while introducing controlled degradable properties into CP-based transient materials. In response to this, we present in this work a concept of using conducting polymers attached to an enzymatically biodegradable biopolymer to create transient polymer electronics materials. Specifically, poly(3-hexyl thiophene) (P3HT) is covalently grafted onto biopolymer gelatin, affording graft copolymer gelatin-graft-poly(3-hexyl thiophene) (termed Gel-g-P3HT). The thin films of Gel-g-P3HT that were produced by optimized processing solvent (THF/H2O cosolvent) showed enhanced π-π stacking domains of P3HT, resulting in semiconducting thin films with good electroactivity. Due to the presence of amide bonds in the gelatin backbone, Gel-g-P3HT underwent degradation over a period of 5 days, resulting in the formation of amphiphilic micellar nanoparticles that are biocompatible and nontoxic. The potential of these conductive and degradable graft copolymers was demonstrated in a pressure sensor. This research paves the way for developing biocompatible and enzymatically degradable polymer materials based on P3HT, enabling the next generation of transient polymer electronics for diverse applications, such as skin, implantable, and environmental electronics.

Using whole genome sequencing to characterize Clostridioides difficile isolates at a tertiary center in Melbourne, Australia.

Objective: Clostridioides difficile infection (CDI) is the commonest cause of healthcare-associated diarrhea and undergoes standardized surveillance and mandatory reporting in most Australian states and territories. Historically attributed to nosocomial spread, local and international whole genome sequencing (WGS) data suggest varied sources of acquisition. This study describes C. difficile genotypes isolated at a tertiary center in Melbourne, Australia, their likely source of acquisition, and common risk factors. Design: Retrospective observational study. Setting: The Royal Melbourne Hospital (RMH), a 570-bed tertiary center in Victoria, Australia. Methods: Short-read whole genome sequencing was performed on 75 out of 137 C. difficile isolates obtained from 1/5/2021 to 28/2/2022 and compared to previous data from 8/11/2015 to 1/11/2016. Existing data from infection control surveillance and electronic medical records were used for epidemiological and risk factor analysis. Results: Eighty-five (62.1%) of the 137 cases were defined as healthcare-associated from epidemiological data. On genome sequencing, 33 different multi-locus sequence type (MLST) subtypes were identified, with changes in population structure compared to the 2015-16 period. Risk factors for CDI were present in 130 (94.9%) cases, including 108 (78.8%) on antibiotics, 86 (62.8%) on acid suppression therapy, and 25 (18.2) on chemotherapy. Conclusion: In both study periods, most C. difficile isolates were not closely related, suggesting varied sources of acquisition and that spread of C. difficile within the hospital was unlikely. Current infection control precautions may therefore warrant review. Underlying risk factors for CDI were common and may contribute to the proportion of healthcare-associated infections in the absence of proven hospital transmission.

Acetylenic tricyclic bis-(cyano enone) interacts with Cys 374 of actin, a residue necessary for stress fiber formation and cell migration.

The migratory and invasive potential of tumour cells relies on the actin cytoskeleton. We previously demonstrated that the tricyclic compound, TBE-31, inhibits actin polymerization and here we further examine the precise interaction between TBE-31 and actin. We demonstrate that iodoacetamide, a cysteine (Cys) alkylating agent, interferes with the ability of TBE-31 to interact with actin. In addition, in silico analysis identified Cys 217, Cys 272, Cys 285 and Cys 374 as potential binding sites for TBE-31. Using mass spectrometry analysis, we determined that TBE-31 associates with actin with a stoichiometric ratio of 1:1. We mutated the identified cysteines of actin to alanine and performed a pull-down analysis with a biotin labeled TBE-31 and demonstrated that by mutating Cys 374 to alanine the association between TBE-31 and actin was significantly reduced, suggesting that TBE-31 binds to Cys 374. A characterization of the NIH3T3 cells overexpressing eGFP-actin-C374A showed reduced stress fiber formation, suggesting Cys 374 is necessary for efficient incorporation into filamentous actin. Furthermore, migration of eGFP-Actin-WT expressing cells were observed to be inhibited by TBE-31, however fewer eGFP-Actin-C374A expressing cells were observed to migrate compared to the cells expressing eGFP-Actin-WT in the presence or absence of TBE-31. Taken together, our results suggest that TBE-31 binds to Cys 374 of actin to inhibit actin stress fiber formation and may potentially be a mechanism through which TBE-31 inhibits cell migration.

Clinical and microbiological characteristics of Staphylococcus lugdunensis.

PURPOSE OF REVIEW: This review provides an update on recent findings about the clinical and microbiological characteristics of Staphylococcus lugdunensis . RECENT FINDINGS: European Committee on Antimicrobial Susceptibility Testing (EUCAST) and Clinical and Laboratory Standards Institute (CLSI) differ in their methodology and breakpoints for the detection of penicillin and oxacillin resistance in S. lugdunensis . The EUCAST method for beta-lactamase detection recommends a 1-unit penicillin disk and has demonstrated superior performance compared to the 10-unit penicillin disk recommended by CLSI. A similar outcome has been previously reported in Staphylococcus aureus. In addition, there is emerging oxacillin resistance in some geographical areas. Of particular concern is that oxacillin resistance in mecA positive isolates may not be reliably detected by current cefoxitin breakpoints. SUMMARY: Coagulase negative staphylococci are now recognised as a heterogenous group of organisms that do not microbiologically or clinically behave the same way. The spectrum of clinical disease is species dependent and is particularly true for S. lugdunensis , which causes an array of clinical infections like that of S. aureus. Further studies are needed to assess the performance of phenotypic tests to detect resistance, to ensure that appropriate antimicrobial therapy is delivered to patients.

Predicting perioperative outcomes of robot-assisted radical cystectomy: Data from the Asian Robot-Assisted Radical Cystectomy Consortium.

OBJECTIVES: To report the perioperative outcomes of robot-assisted radical cystectomy and elucidate their risk factors. METHODS: A review of the Asian Robot-Assisted Radical Cystectomy Consortium database from 2007 to 2020 was performed. The perioperative outcomes studied included complication rates, time to solid food intake, estimated blood loss, length of hospital stay, and 30-day readmission rates. RESULTS: Of 568 patients, the overall complication rate was 49.2%, comprising major complications in 15.6%. Preoperative hydronephrosis was associated with an increased risk of major complications (odds ratio 3.27, 95% confidence interval 1.48-7.26, P = 0.004) while neoadjuvant chemotherapy was protective (odds ratio 0.46, 95% confidence interval 0.25-0.84, P = 0.012). The median time to solid food intake was 4 days (interquartile range 3-7) and smoking was a risk factor (odds ratio 4.28, 95% confidence interval 2.36-7.79, P < 0.001) for prolonged time to solid food intake. Median length of hospital stay was 13 days (interquartile range 9-19), and diabetes mellitus (odds ratio 1.66, 95% confidence interval 1.08-2.56, P = 0.021), neoadjuvant chemotherapy (odds ratio 2.21, 95% confidence interval 1.46-3.33, P < 0.001), and orthotopic bladder substitute creation (odds ratio 2.82, 95% confidence interval 1.90-4.18, P < 0.001) were independent risk factors for prolonged length of hospital stay. The 30-day readmission rate was 23.4% and higher in those with bilateral hydronephrosis (odds ratio 4.58, 95% confidence interval 1.97-10.65, P < 0.001) and orthotopic bladder substitute creation (odds ratio 1.87, 95% confidence interval 1.16-3.02, P = 0.010). CONCLUSIONS: There are preoperative conditions which are significant risk factors for adverse perioperative outcomes in robot-assisted radical cystectomy. Most are potentially modifiable and can direct strategies to reduce surgical morbidity related to this major oncological procedure.

Toward cheaper light harvesting systems: Using earth-abundant metal oxide nanoparticles in self-assembled peptide-porphyrin nanofibers.

Cheap artificial light harvesting systems, which competently harvest solar energy and promote efficient energy transfer, are highly sought after in the renewable sector. We report the synthesis of self-assembled peptide-porphyrin fibers (SJ 6) fabricated with iron(III) oxide (Fe3 O4 ) nanoparticles as feasible electron acceptors. Charge-complementarity between the negatively charged peptide (20E) and the protonated Zn-tetraphenyl porphyrin (ZnTPyP) led to an ordered assembly of the ZnTPyP molecules, enabling efficient light harvesting. X-ray diffraction data indicates a more ordered structure in SJ 6 compared to 20E and ZnTPyP. The incorporation of Fe3 O4 nanoparticles into SJ 6 showed significant fluorescence quenching, indicating efficient electron flow from the donor to the acceptor. The SJ 6-nFe3 O4 system performed the light reaction of photosynthesis as confirmed by the reduction of 1 mM NAD+ to 0.180 mM NADH upon exposure to visible light (Xe lamp λ > 420 nm) for 1 h. The photochemical regeneration of NADH using the SJ 6-nFe3 O4 system was coupled to glutamate dehydrogenase-catalyzed conversion of α-ketoglutarate to L-glutamate. These results confirm the successful synthesis of an artificial light harvesting peptide-porphyrin system with Fe3 O4 nanoparticles as promising low-cost electron separators.

Active video game on children and adolescents' physical activity and weight management: A network meta-analysis.

We synthesized evidence on the effectiveness of active video games (AVGs) versus no AVG-applied comparators on various physical activity (PA) levels and weight management outcomes in children and adolescents. We analyzed the comparative evidence on different sub-categories of AVGs and ranking the best option. An overview of systematic reviews (SRs) and network meta-analysis (NMA) (PROSPERO: CRD42021248499) was employed. A search for relevant literature published in English was conducted in six electronic databases from their inception until April 2021. SRs consisting of randomized control trials (RCTs) and satisfying our PICOS inclusion criteria were included. RCTs included were a comparison of groups among children and adolescents between 6 and 21, where groups with AVG interventions were compared with groups without them. Direct head-to-head pairwise meta-analyses were conducted using weighted mean difference between the two groups, and the comparative effectiveness of different sub-categories of AVGs was analyzed indirectly using NMA. Overall, 17 SRs were identified from the 6036 screened citations. Of these, 350 citations were retrieved, and 12 RCTs were finally included. Compared with no AVG group, AVG groups were shown to be more effective in achieving vigorous, moderate-to-vigorous, and moderate PA levels, and decreased BMI and body fat. NMA showed that rhythmic dance games had the highest probability of being the most effective sub-category for reducing BMI. AVGs are effective in attaining vigorous, moderate to vigorous, and moderate PA levels, and reducing BMI and body fat among children and adolescents. Dance appears to be the best option for reducing BMI among AVG subcategories.

Perioperative Outcomes of Robot-Assisted Radical Cystectomy with Intracorporeal Versus Extracorporeal Urinary Diversion.

PURPOSE: This study was designed to investigate and compare the perioperative outcomes of intracorporeal urinary diversion (ICUD) versus extracorporeal urinary diversion (ECUD) following robotic-assisted radical cystectomy (RARC) in patients with localized bladder cancer from the Asian Robot-Assisted Radical Cystectomy (RARC) Consortium. METHODS: The Asian RARC registry was a multicenter registry involving nine centers in Asia. Consecutive patients who underwent RARC were included. Patient and disease characteristics, intraoperative details, and perioperative outcomes were reviewed and compared between the ICUD and ECUD groups. Postoperative complications were the primary outcomes, whereas secondary outcomes were the estimated blood loss and the duration of hospitalization. Multivariate regression analyses were performed to adjust potential confounders. RESULTS: From 2007 to 2020, 556 patients underwent RARC; 55.2% and 44.8% had ICUD and ECUD, respectively. ICUD group had less estimated blood loss (423.1 ± 361.1 vs. 541.3 ± 474.3 mL, p = 0.002) and a shorter hospital stay (15.7 ± 12.3 vs 17.8 ± 11.6 days, p = 0.042) than the ECUD group. Overall complication rates were similar between the two groups. Upon multivariate analysis, ICUD was associated with less estimated blood loss (Regression coefficient: - 143.06, 95% confidence interval [CI]: - 229.60 to - 56.52, p = 0.001) and a shorter hospital stay (Regression coefficient: - 2.37, 95% CI: - 4.69 to - 0.05, p = 0.046). In addition, ICUD was not associated with any increased risks of minor, major, and overall complications. CONCLUSIONS: RARC with ICUD was safe and technically feasible with similar postoperative complication rates as ECUD, with additional benefits of reduced blood loss and a shorter hospitalization.

Evaluation of the VITEK 2 Advanced Expert System performance for predicting resistance mechanisms in Enterobacterales acquired from a hospital-based screening program.

There is limited literature examining the accuracy of the VITEK 2 Advanced Expert System (AES) in characterisation of ß-lactamase resistance patterns. We present a prospective single centre study to better ascertain the performance characteristics of this program. The VITEK 2 AES interpretation was compared to established laboratory phenotypic methods. The overall sensitivity for detection of broad-spectrum ß-lactamase by the AES was 95%, with a specificity of 78%. One or more discrepancies were noted in 36% of samples, with the majority of these (87/100) due to incorrect 'overcall' of a resistance mechanism. AES characterisation of AmpC resistance mechanisms was excellent. In contrast, the AES had poor specificity in classifying extended spectrum ß-lactamases (ESBLs). As a screening aid, the AES can be a valuable tool. However, optimal use requires an adequate working knowledge of resistance mechanisms in order to correctly interpret and accept the result output.

Consensus statements on the management of metastatic renal cell carcinoma from the Hong Kong Urological Association and the Hong Kong Society of Uro-Oncology 2019.

BACKGROUND: To establish a set of consensus statements for the management of metastatic renal cell carcinoma, a total of 12 urologists and clinical oncologists from two professional associations in Hong Kong formed an expert consensus panel. METHODS: Through a series of meetings and using the modified Delphi method, the panelists presented recent evidence, discussed clinical experiences, and drafted consensus statements on several areas of focus regarding the management of metastatic renal cell carcinoma. Each statement was eventually voted upon by every panelist based on the practicability of recommendation. RESULTS: A total of 46 consensus statements were ultimately accepted and established by panel voting. CONCLUSIONS: Derived from recent evidence and expert insights, these consensus statements were aimed at providing practical guidance to optimize metastatic renal cell carcinoma management and promote a higher standard of clinical care.

Electroactive Metal Complexes Covalently Attached to Conductive PEDOT Films: A Spectroelectrochemical Study.

The successful covalent attachment, via copper(I)-catalyzed azide alkyne cycloaddition (CuAAC), of alkyne-functionalized nickel(II) and copper(II) macrocyclic complexes onto azide (N3)-functionalized poly(3,4-ethylenedioxythiophene) (PEDOT) films on ITO-coated glass electrodes is reported. To investigate the surface attachment of the selected metal complexes, which are analogues of the cobalt-based complex previously reported to be a molecular catalyst for hydrogen evolution, first, three different PEDOT films were formed by electropolymerization of pure PEDOT or pure N3-PEDOT, and last, 1:2N3-PEDOT:PEDOT were formed by co-polymerizing a 1:4 mixture of N3-EDOT:EDOT monomers. The successful surface immobilization of the complexes on the latter two azide-functionalized films, by CuAAC, was confirmed by X-ray photoelectron spectroscopy (XPS) and electrochemistry as well as by UV-vis-NIR and resonance Raman spectroelectrochemistry. The ratio between the N3 groups, and hence, the number of surface-attached metal complexes after CuAAC functionalization, in pristine N3-PEDOT versus 1:2N3-PEDOT:PEDOT is expected to be 3:1 and seen to be 2.86:1 with a calculated surface coverage of 3.28 ± 1.04 and 1.15 ± 0.09 nmol/cm2, respectively. The conversion, to the metal complex attached films, was lower for the N3-PEDOT films (Ni 74%, Cu 76%) than for the copolymer 1:2N3-PEDOT:PEDOT films (Ni 83%, Cu 91%) due to the former being more sterically congested. The Raman and UV-vis-NIR results were simulated using density functional theory (DFT) and time-dependent DFT (TD-DFT), respectively, and showed good agreement with the experimental data. Importantly, the spectroelectrochemical behavior of both anchored metal complexes is analogous to that of the free metal complexes in solution. This proves that PEDOT films are promising conducting scaffolds for the covalent immobilization of metal complexes, as the existing electrochromic features of the complexes are preserved on immobilization, which is important for applications in electrocatalytic proton and carbon dioxide reduction, optoelectronics, and sensing.

Current evidence for robotic surgery in radical cystectomy.

Robotic-assisted radical cystectomy (RARC) has been gaining momentum as an alternative to its conventional open radical cystectomy (ORC) for the management of invasive bladder cancer. Although RARC, in general, demonstrated less blood loss and shorter hospital stay than ORC, whether there is any significant difference in the overall complication rate still requires further investigation. Thus, both RARC and ORC share a similar oncology outcome, with comparable positive surgical margin rates, disease-free survival, and overall survival. Techniques of intracorporeal urinary diversion (ICUD) have not yet been standardized. ICUD may result in a lower risk of ureteroileal anastomotic stricture than extracorporeal urinary diversion (ECUD). However, ECUD is still a valid and commonly practiced option according to the available data. In general, RARC has been demonstrated to provide promising results. Long-term data and functional outcome after RARC and ICUD are needed to further validate the role of RARC in the management of bladder cancer.

Surgical training for anatomical endoscopic enucleation of the prostate.

Anatomical endoscopic enucleation of the prostate has been proposed as a potentially superior benign prostatic hyperplasia surgery than conventional transurethral resection of prostate. However, the learning curve of the procedure is steep, hence limiting its generalisability worldwide. In order to overcome the learning curve, a proper surgical training is extremely important. This review article discussed about various aspects of surgical training in anatomical endoscopic enucleation of the prostate. In summary, no matter what surgical technique or energy modality you use, the principle of anatomical enucleation should be followed. When one starts to perform prostate enucleation, a 50 to 80 g prostate appears to be the 'best case' to begin with. Mentorship is extremely important to shorten the learning curve and to prevent drastic complications from the procedure. A proficiency-based progression training programme with the use of simulation and training models should be the best way to teach and learn about prostate enucleation. Enucleation ratio efficacy is the preferred measure for assessing skill level and learning curve of prostate enucleation. Morcellation efficiency is commonly used to assess morcellation performance, but the importance of safety rather than efficiency must be emphasised.

SMURF2 and SMAD7 induce SARA degradation via the proteasome.

TGFß-dependent signal transduction is facilitated by Smad anchor for receptor activation (SARA) and inhibited by the inhibitory-Smad, Smad7, which recruits the E3 ubiquitin ligase, Smurf2, to catalyze the degradation of TGFß receptors. Since the signalling and degradation pathways target active receptor complexes, we assessed if SARA and Smurf2/Smad7 interact and if Smad7/Smurf2 would affect SARA steady state levels. We observed that the Smurf2/Smad7 complex induces a decrease of SARA steady state levels in a process that is dependent on the HECT ubiquitin E3 ligase activity of Smurf2 but is independent of SARA associating with TGFß receptors or Smad2. We observed that Smurf2/Smad7-dependent reduction of SARA levels is dependent on proteasome activity, as the pharmacological inhibition of the proteasome using MG132 blocked degradation of SARA. When we assessed the functional outcome of reducing endogenous SARA levels via siRNA-mediated silencing, we observed that siRNA directed at SARA decreased both TGFß-dependent Smad2 membrane recruitment and phosphorylation, as assessed by subcellular fractionation and western blotting. Furthermore, siRNA targeting SARA decreased TGFß-dependent epithelial to mesenchymal transition, as measured by cellular E- and N-Cadherin protein levels, and the reorganization of actin from cortical actin to stress fiber formation. These data describe a previously undescribed mechanism where the robustness of the TGFß signalling is regulated by interplay between SARA and Smurf2/Smad7 complexes.