A germline point mutation in the MYC-FBW7 phosphodegron initiates hematopoietic malignancies.

Oncogenic activation of MYC in cancers predominantly involves increased transcription rather than coding region mutations. However, MYC-dependent lymphomas frequently acquire point mutations in the MYC phosphodegron, including at threonine 58 (T58), where phosphorylation permits binding via the FBW7 ubiquitin ligase triggering MYC degradation. To understand how T58 phosphorylation functions in normal cell physiology, we introduced an alanine mutation at T58 (T58A) into the endogenous c-Myc locus in the mouse germline. While MYC-T58A mice develop normally, lymphomas and myeloid leukemias emerge in ∼60% of adult homozygous T58A mice. We found that primitive hematopoietic progenitor cells from MYC-T58A mice exhibit aberrant self-renewal normally associated with hematopoietic stem cells (HSCs) and up-regulate a subset of MYC target genes important in maintaining stem/progenitor cell balance. In lymphocytes, genomic occupancy by MYC-T58A was increased at all promoters compared with WT MYC, while genes differentially expressed in a T58A-dependent manner were significantly more proximal to MYC-bound enhancers. MYC-T58A lymphocyte progenitors exhibited metabolic alterations and decreased activation of inflammatory and apoptotic pathways. Our data demonstrate that a single point mutation stabilizing MYC is sufficient to skew target gene expression, producing a profound gain of function in multipotential hematopoietic progenitors associated with self-renewal and initiation of lymphomas and leukemias.

A hexasome is the preferred substrate for the INO80 chromatin remodeling complex, allowing versatility of function.

The critical role of the INO80 chromatin remodeling complex in transcription is commonly attributed to its nucleosome sliding activity. Here, we have found that INO80 prefers to mobilize hexasomes over nucleosomes. INO80's preference for hexasomes reaches up to ∼60 fold when flanking DNA overhangs approach ∼18-bp linkers in yeast gene bodies. Correspondingly, deletion of INO80 significantly affects the positions of hexasome-sized particles within yeast genes in vivo. Our results raise the possibility that INO80 promotes nucleosome sliding by dislodging an H2A-H2B dimer, thereby making a nucleosome transiently resemble a hexasome. We propose that this mechanism allows INO80 to rapidly mobilize nucleosomes at promoters and hexasomes within gene bodies. Rapid repositioning of hexasomes that are generated in the wake of transcription may mitigate spurious transcription. More generally, such versatility may explain how INO80 regulates chromatin architecture during the diverse processes of transcription, replication, and repair.

At least two to tango: Choreographing chromatin through cooperative footprints.

Two recent papers, Rao et al. (2021), in this issue, and Sönmezer et al. (2021), investigate transcription factor cooperativity at cis-regulatory elements. Using data from nuclease- and methyltransferase-footprinting experiments, they demonstrate that factor co-occupancy at regulatory elements commonly occurs in vivo and is conserved from fly to mouse.

The glucose-sensing transcription factor MLX balances metabolism and stress to suppress apoptosis and maintain spermatogenesis.

Male germ cell (GC) production is a metabolically driven and apoptosis-prone process. Here, we show that the glucose-sensing transcription factor (TF) MAX-Like protein X (MLX) and its binding partner MondoA are both required for male fertility in the mouse, as well as survival of human tumor cells derived from the male germ line. Loss of Mlx results in altered metabolism as well as activation of multiple stress pathways and GC apoptosis in the testes. This is concomitant with dysregulation of the expression of male-specific GC transcripts and proteins. Our genomic and functional analyses identify loci directly bound by MLX involved in these processes, including metabolic targets, obligate components of male-specific GC development, and apoptotic effectors. These in vivo and in vitro studies implicate MLX and other members of the proximal MYC network, such as MNT, in regulation of metabolism and differentiation, as well as in suppression of intrinsic and extrinsic death signaling pathways in both spermatogenesis and male germ cell tumors (MGCTs).

Cost-effectiveness model of renal cell carcinoma (RCC) surveillance in hereditary leiomyomatosis and renal cell carcinoma (HLRCC).

PURPOSE: To determine the cost-effectiveness of annual renal imaging surveillance (RIS) in hereditary leiomyomatosis and renal cell cancer (HLRCC). HLRCC is associated with a 21% risk to age 70 years of RCC. Presentations with advanced renal cell cancer (RCC) are associated with poor outcomes whereas RIS detects early-stage RCC; however, evidence for the cost-effectiveness of RIS is lacking. METHODS: We developed a decision-analytic model to compare, at different age starting points (11 years, 18 years, 40 years, 60 years), the costs and benefits of lifetime contrast-enhanced renal MRI surveillance (CERMRIS) vs no surveillance in HLRCC. Benefits were measured in life-years gained (LYG), quality-adjusted life years (QALYs) and costs in British Pounds Sterling (GBP). Net monetary benefit (NMB) was calculated using a cost-effectiveness threshold of £20 000/QALY. One-way sensitivity and probabilistic analyses were also performed. RESULTS: In the base-case 11-year age cohort, surveillance was cost-effective (Incremental_NMB=£3522 (95% CI -£2747 to £7652); Incremental_LYG=1.25 (95% CI 0.30 to 1.86); Incremental_QALYs=0.29 (95% CI 0.07 to 0.43)] at an additional mean discounted cost of £2185/patient (95% CI £430 to £4144). Surveillance was also cost-effective in other age cohorts and dominated a no surveillance strategy in the 40 year cohort [Incremental_NMB=£12 655 (95% CIs -£709 to £21 134); Incremental_LYG=1.52 (95% CI 0.30 to 2.26); Incremental_QALYs=0.58 (95% CI 0.12 to 0.87) with a cost saving of £965/patient (95% CI -£4202 to £2652). CONCLUSION: Annual CERMRI in HLRCC is cost-effective across age groups modelled.

Electrochemical implications of modulating the solvation shell around redox active organic species in aqueous organic redox flow batteries.

Organic and organometallic reactants in aqueous electrolytes, being composed of earth-abundant elements, are promising redox active candidates for cost-effective organic redox flow batteries (ORFBs). Various compounds of ferrocene and methyl viologen have been examined as promising redox actives for this application. Herein, we examined the influence of the electrolyte pH and the salt anion on model redox active organic cations, bis((3-trimethylammonio) propyl)- ferrocene dichloride (BTMAP-Fc) and bis(3-trimethylammonio) propyl viologen tetrachloride (BTMAP-Vi), which have exhibited excellent cycling stability and capacity retention at ≥1.00 M concentration [E. S. Beh, et al. ACS Energy Lett. 2, 639-644 (2017)]. We examined the solvation shell around BTMAP-Fc and BTMAP-Vi at acidic and neutral pH with SO42-, Cl-, and CH3SO3- counterions and elucidated their impact on cation diffusion coefficient, first electron transfer rate constant, and thereby the electrochemical Thiele modulus. The electrochemical Thiele modulus was found to be exponentially correlated with the solvent reorganizational energy (λ) in both neutral and acidic pH. Thus, λ is proposed as a universal descriptor and selection criteria for organic redox flow battery electrolyte compositions. In the specific case of the BTMAP-Fc/BTMAP-Vi ORFB, low pH electrolytes with methanesulfonate or chloride counterions were identified as offering the best balance of transport and kinetic requirements.

High-performance AEM unitized regenerative fuel cell using Pt-pyrochlore as bifunctional oxygen electrocatalyst.

The performance of fixed-gas unitized regenerative fuel cells (FG-URFCs) are limited by the bifunctional activity of the oxygen electrocatalyst. It is essential to have a good bifunctional oxygen electrocatalyst which can exhibit high activity for oxygen evolution reaction (OER) and oxygen reduction reaction (ORR). In this regard, Pt-Pb2Ru2O7-x is synthesized by depositing Pt on Pb2Ru2O7-x wherein Pt individually exhibits high ORR while Pb2Ru2O7-x shows high OER and moderate ORR activity. Pt-Pb2Ru2O7-x exhibits higher OER (η@10mAcm-2 = 0.25 ± 0.01 V) and ORR (η@-3mAcm-2 = -0.31 ± 0.02 V) activity in comparison to benchmark OER (IrO2, η@10mAcm-2 = 0.35 ± 0.02 V) and ORR (Pt/C, η@-3mAcm-2 = -0.33 ± 0.02 V) electrocatalysts, respectively. Pt-Pb2Ru2O7-x shows a lower bifunctionality index (η@10mAcm-2, OER- η@-3mAcm-2, ORR) of 0.56 V with more symmetric OER-ORR activity profile than both Pt (>1.0 V) and Pb2Ru2O7-x (0.69 V) making it more useful for the AEM (anion exchange membrane) URFC or metal-air battery applications. FG-URFC tested with Pt-Pb2Ru2O7-x and Pt/C as bifunctional oxygen electrocatalyst and bifunctional hydrogen electrocatalyst, respectively, yields a mass-specific current density of 715 ± 11 A/gcat-1 at 1.8 V and 56 ± 2 A/gcat-1 at 0.9 V under electrolyzer mode and fuel-cell mode, respectively. The FG-URFC shows a round-trip efficiency of 75% at 0.1 A/cm-2, underlying improvement in AEM FG-URFC electrocatalyst design.

Involvement of endoplasmic reticulum and histone proteins in immunomodulation by TLR4-interacting SPA4 peptide against Escherichia coli.

Pulmonary host defense is critical for the control of lung infection and inflammation. An increased expression and activity of Toll-like receptor 4 (TLR4) induce phagocytic uptake/clearance and inflammation against Gram-negative bacteria. In this study, we addressed the mechanistic aspect of the immunomodulatory activity of the TLR4-interacting SPA4 peptide (amino acid sequence GDFRYSDGTPVNYTNWYRGE) against Escherichia coli. Binding of the SPA4 peptide to bacteria and direct anti-bacterial effects were investigated using flow cytometric, microscopic, and bacteriological methods. The bacterial uptake and inflammatory cytokine response were studied in dendritic cells expressing endogenous basal level of TLR4 or overexpressing TLR4. The subcellular distribution and co-localization of TLR4 and bacteria were investigated by immunocytochemistry. Furthermore, we studied the cellular expression and co-localization of endoplasmic reticulum (ER) molecules (calnexin and ER membrane protein complex subunit 1; EMC1) with lysosomal-associated membrane protein 1 (LAMP1) in cells infected with E. coli and treated with the SPA4 peptide. Simultaneously, the expression of histone H2A protein was quantitated by immunoblotting. Our results demonstrate no binding or direct killing of the bacteria by SPA4 peptide. Instead, it induces the uptake and localization of E. coli in the phagolysosomes for lysis and simultaneously suppresses the secreted levels of TNF-α. Overexpression of TLR4 further augments the pro-phagocytic and anti-inflammatory activity of SPA4 peptide. A time-dependent change in subcellular distribution of TLR4 and an increased co-localization of TLR4 with E. coli in SPA4 peptide-treated cells suggest an enhanced recognition and internalization of bacteria in conjugation with TLR4. Furthermore, an increased co-localization of calnexin and EMC1 with LAMP1 indicates the involvement of ER in pro-phagocytic activity of SPA4 peptide. Simultaneous reduction in secreted amounts of TNF-α coincides with suppressed histone H2A protein expression in the SPA4 peptide-treated cells. These results provide initial insights into the plausible role of ER and histones in the TLR4-immunomodulatory activity of SPA4 peptide against Gram-negative bacteria.

Pyrochlores for Advanced Oxygen Electrocatalysis.

Fuel cells (FCs), water electrolyzers (WEs), unitized regenerative fuel cells (URFCs), and metal-air batteries (MABs) are among the emerging electrochemical technologies for energy storage, fuel (H2), oxidant (O2), and clean energy production. Their commercial applications are hindered by the low oxygen reduction reaction/oxygen evolution reaction (ORR/OER) bifunctional activity (for URFCs and MABs), OER selectivity (brine electrolysis in seawater and Martian environments), and high cost of the benchmark electrocatalysts (OER: RuO2, IrO2 and ORR: Pt/C) which affects the performance and affordability of the devices. Low-cost electrocatalysts with highly symmetric ORR/OER bifunctional activity and high OER selectivity are crucial for large-scale FC, WE, URFC, and MAB application. Recent studies have revealed that tuning the structure of pyrochlore oxides provides a pathway to enhancing OER and ORR activity over a wide range of pH. Pyrochlore oxides commonly contain a cubic A2B2O7-x structure with two types of tetrahedrally coordinated O atoms containing (1) A-O-A and (2) A-O-B types with a cationic radii mismatch of rA/rB > 1.5 and propensity toward oxygen vacancy formation. The variety of pyrochlore oxides and their tunable properties make them attractive for a wide spectrum of applications. Among all the metal oxides, Ru-based pyrochlores (e.g., Pb2Ru2O7-x) exhibit the best bifunctional oxygen electrocatalytic activity, i.e., low bifunctionality index (BI), in alkaline medium. Furthermore, pyrochlores exhibit high OER selectivity in brine electrolytes due to the presence of surface oxygen vacancies, making them suitable for space applications (brine electrolysis on Mars) and coastal hydrogen generation. Their bifunctional activity and selectivity can be further amplified by (1) substituting "A" and "B" sites of pyrochlores (AA'BB'O7-x), (2) tuning metal oxidation states of A and B by varying synthesis conditions, and (3) modulating oxygen vacancy concentration, each of which yield favorable structural and electronic variations. In recent years, research on the synthesis and understanding of pyrochlores has significantly enhanced their viability, offering a new horizon in the quest for economical and active electrocatalysts. However, an account that focuses on critical developments in this field is still lacking.In this Account, we focus on the recent development of a variety of pyrochlore electrocatalysts to understand intrinsic structure-activity-selectivity-stability relationships in these materials. Recent developments and applications of pyrochlore-based electrocatalysts are discussed under the following headings: (1) modulation of crystal and electronic structure of pyrochlores, (2) structure-activity-stability relationships of different pyrochlores for OER and ORR, (3) development of OER-selective pyrochlores for brine electrolysis, and (4) the application of pyrochlores in electrochemical devices. Finally, we highlight some unaddressed issues such as the precise identification of active sites, which can be addressed in the future through advanced in situ and ex situ characterization techniques coupled with the density functional theory-based analyses. This Account provides foundational understanding to guide the comprehensive development of highly active, selective, stable and low-cost structurally engineered pyrochlores for high performance electrochemical devices.

Fuel and oxygen harvesting from Martian regolithic brine.

NASA's current mandate is to land humans on Mars by 2033. Here, we demonstrate an approach to produce ultrapure H2 and O2 from liquid-phase Martian regolithic brine at ∼-36 °C. Utilizing a Pb2Ru2O7-δ pyrochlore O2-evolution electrocatalyst and a Pt/C H2-evolution electrocatalyst, we demonstrate a brine electrolyzer with >25× the O2 production rate of the Mars Oxygen In Situ Resource Utilization Experiment (MOXIE) from NASA's Mars 2020 mission for the same input power under Martian terrestrial conditions. Given the Phoenix lander's observation of an active water cycle on Mars and the extensive presence of perchlorate salts that depress water's freezing point to ∼-60 °C, our approach provides a unique pathway to life-support and fuel production for future human missions to Mars.

Radiotherapy to the prostate for men with metastatic prostate cancer in the UK and Switzerland: Long-term results from the STAMPEDE randomised controlled trial.

BACKGROUND: STAMPEDE has previously reported that radiotherapy (RT) to the prostate improved overall survival (OS) for patients with newly diagnosed prostate cancer with low metastatic burden, but not those with high-burden disease. In this final analysis, we report long-term findings on the primary outcome measure of OS and on the secondary outcome measures of symptomatic local events, RT toxicity events, and quality of life (QoL). METHODS AND FINDINGS: Patients were randomised at secondary care sites in the United Kingdom and Switzerland between January 2013 and September 2016, with 1:1 stratified allocation: 1,029 to standard of care (SOC) and 1,032 to SOC+RT. No masking of the treatment allocation was employed. A total of 1,939 had metastatic burden classifiable, with 42% low burden and 58% high burden, balanced by treatment allocation. Intention-to-treat (ITT) analyses used Cox regression and flexible parametric models (FPMs), adjusted for stratification factors age, nodal involvement, the World Health Organization (WHO) performance status, regular aspirin or nonsteroidal anti-inflammatory drug (NSAID) use, and planned docetaxel use. QoL in the first 2 years on trial was assessed using prospectively collected patient responses to QLQ-30 questionnaire. Patients were followed for a median of 61.3 months. Prostate RT improved OS in patients with low, but not high, metastatic burden (respectively: 202 deaths in SOC versus 156 in SOC+RT, hazard ratio (HR) = 0·64, 95% CI 0.52, 0.79, p < 0.001; 375 SOC versus 386 SOC+RT, HR = 1.11, 95% CI 0.96, 1.28, p = 0·164; interaction p < 0.001). No evidence of difference in time to symptomatic local events was found. There was no evidence of difference in Global QoL or QLQ-30 Summary Score. Long-term urinary toxicity of grade 3 or worse was reported for 10 SOC and 10 SOC+RT; long-term bowel toxicity of grade 3 or worse was reported for 15 and 11, respectively. CONCLUSIONS: Prostate RT improves OS, without detriment in QoL, in men with low-burden, newly diagnosed, metastatic prostate cancer, indicating that it should be recommended as a SOC. TRIAL REGISTRATION: ClinicalTrials.gov NCT00268476, ISRCTN.com ISRCTN78818544.

Tuning anion solvation energetics enhances potassium-oxygen battery performance.

The oxygen reduction reaction (ORR) is a critical reaction in secondary batteries based on alkali metal chemistries. The nonaqueous electrolyte mediates ion and oxygen transport and determines the heterogeneous charge transfer rates by controlling the nature and degree of solvation. This study shows that the solvent reorganization energy (λ) correlates well with the oxygen diffusion coefficient [Formula: see text] and with the ORR rate constant [Formula: see text] in nonaqueous Li-, Na-, and K-O2 cells, thereby elucidating the impact of variations in the solvation shell on the ORR. Increasing cation size (from Li+ to K+) doubled [Formula: see text], indicating an increased sensitivity of k to the choice of anion, while variations in [Formula: see text]were minimal over this cation size range. At the level of a symmetric K-O2 cell, both the formation of solvent-separated ion pairs [K+-(DMSO)n-ClO4- + (DMSO)m-ClO4-] and the anions being unsolvated (in case of PF6-) lowered ORR activation barriers with a 200-mV lower overpotential for the PF6- and ClO4- electrolytes compared with OTf- and TFSI- electrolytes with partial anion solvation [predominantly K+-(DMSO)n-OTf-]. Balancing transport and kinetic requirements, KPF6 in DMSO is identified as a promising electrolyte for K-O2 batteries.

Capturing cell type-specific chromatin compartment patterns by applying topic modeling to single-cell Hi-C data.

Single-cell Hi-C (scHi-C) interrogates genome-wide chromatin interaction in individual cells, allowing us to gain insights into 3D genome organization. However, the extremely sparse nature of scHi-C data poses a significant barrier to analysis, limiting our ability to tease out hidden biological information. In this work, we approach this problem by applying topic modeling to scHi-C data. Topic modeling is well-suited for discovering latent topics in a collection of discrete data. For our analysis, we generate nine different single-cell combinatorial indexed Hi-C (sci-Hi-C) libraries from five human cell lines (GM12878, H1Esc, HFF, IMR90, and HAP1), consisting over 19,000 cells. We demonstrate that topic modeling is able to successfully capture cell type differences from sci-Hi-C data in the form of "chromatin topics." We further show enrichment of particular compartment structures associated with locus pairs in these topics.

Sci-Hi-C: A single-cell Hi-C method for mapping 3D genome organization in large number of single cells.

The highly dynamic nature of chromosome conformation and three-dimensional (3D) genome organization leads to cell-to-cell variability in chromatin interactions within a cell population, even if the cells of the population appear to be functionally homogeneous. Hence, although Hi-C is a powerful tool for mapping 3D genome organization, this heterogeneity of chromosome higher order structure among individual cells limits the interpretive power of population based bulk Hi-C assays. Moreover, single-cell studies have the potential to enable the identification and characterization of rare cell populations or cell subtypes in a heterogeneous population. However, it may require surveying relatively large numbers of single cells to achieve statistically meaningful observations in single-cell studies. By applying combinatorial cellular indexing to chromosome conformation capture, we developed single-cell combinatorial indexed Hi-C (sci-Hi-C), a high throughput method that enables mapping chromatin interactomes in large number of single cells. We demonstrated the use of sci-Hi-C data to separate cells by karytoypic and cell-cycle state differences and to identify cellular variability in mammalian chromosomal conformation. Here, we provide a detailed description of method design and step-by-step working protocols for sci-Hi-C.

Massively multiplex single-cell Hi-C.

We present single-cell combinatorial indexed Hi-C (sciHi-C), a method that applies combinatorial cellular indexing to chromosome conformation capture. In this proof of concept, we generate and sequence six sciHi-C libraries comprising a total of 10,696 single cells. We use sciHi-C data to separate cells by karyotypic and cell-cycle state differences and identify cell-to-cell heterogeneity in mammalian chromosomal conformation. Our results demonstrate that combinatorial indexing is a generalizable strategy for single-cell genomics.

Anisotropy of Pt nanoparticles on carbon- and oxide-support and their structural response to electrochemical oxidation probed by in situ techniques.

Identifying the structural response of nanoparticle-support ensembles to the reaction conditions is essential to determine their structure in the catalytically active state as well as to unravel the possible degradation pathways. In this work, we investigate the (electronic) structure of carbon- and oxide-supported Pt nanoparticles during electrochemical oxidation by in situ X-ray diffraction, absorption spectroscopy as well as the Pt dissolution rate by in situ mass spectrometry. We prepared ellipsoidal Pt nanoparticles by impregnation of the carbon and titanium-based oxide support as well as spherical Pt nanoparticles on an indium-based oxide support by a surfactant-assisted synthesis route. During electrochemical oxidation, we show that the oxide-supported Pt nanoparticles resist (bulk) oxide formation and Pt dissolution. The lattice of smaller Pt nanoparticles exhibits a size-induced lattice contraction in the as-prepared state with respect to bulk Pt but it expands reversibly during electrochemical oxidation. This expansion is suppressed for the Pt nanoparticles with a bulk-like relaxed lattice. We could correlate the formation of d-band vacancies in the metallic Pt with Pt lattice expansion. PtOx formation is strongest for platelet-like nanoparticles and we explain this with a higher fraction of exposed Pt(100) facets. Of all investigated nanoparticle-support ensembles, the structural response of RuO2/TiO2-supported Pt nanoparticles is the most promising with respect to their morphological and structural integrity under electrochemical reaction conditions.

Platinum supported on titanium-ruthenium oxide is a remarkably stable electrocatayst for hydrogen fuel cell vehicles.

We report a unique and highly stable electrocatalyst-platinum (Pt) supported on titanium-ruthenium oxide (TRO)-for hydrogen fuel cell vehicles. The Pt/TRO electrocatalyst was exposed to stringent accelerated test protocols designed to induce degradation and failure mechanisms identical to those seen during extended normal operation of a fuel cell automobile-namely, support corrosion during vehicle startup and shutdown, and platinum dissolution during vehicle acceleration and deceleration. These experiments were performed both ex situ (on supports and catalysts deposited onto a glassy carbon rotating disk electrode) and in situ (in a membrane electrode assembly). The Pt/TRO was compared against a state-of-the-art benchmark catalyst-Pt supported on high surface-area carbon (Pt/HSAC). In ex situ tests, Pt/TRO lost only 18% of its initial oxygen reduction reaction mass activity and 3% of its oxygen reduction reaction-specific activity, whereas the corresponding losses for Pt/HSAC were 52% and 22%. In in situ-accelerated degradation tests performed on membrane electrode assemblies, the loss in cell voltage at 1 A · cm(-2) at 100% RH was a negligible 15 mV for Pt/TRO, whereas the loss was too high to permit operation at 1 A · cm(-2) for Pt/HSAC. We clearly show that electrocatalyst support corrosion induced during fuel cell startup and shutdown is a far more potent failure mode than platinum dissolution during fuel cell operation. Hence, we posit that the need for a highly stable support (such as TRO) is paramount. Finally, we demonstrate that the corrosion of carbon present in the gas diffusion layer of the fuel cell is only of minor concern.

Is it safe to insert a testicular prosthesis at the time of radical orchidectomy for testis cancer: an audit of 904 men undergoing radical orchidectomy.

OBJECTIVE: To compare the complication rate associated with synchronous prosthesis insertion at the time of radical orchidectomy with orchidectomy alone. PATIENT AND METHODS: All men undergoing radical orchidectomy for testis cancer in the North West Region of England between April 1999 to July 2005 and November 2007 to November 2009 were included. Data on postoperative complications, length of stay (LOS), re-admission rate and return to theatre rate were collected. RESULTS: In all, 904 men [median (range) age 35 (14-88) years], underwent a radical orchidectomy during the study period and 413 (46.7%) were offered a prosthesis, of whom 55.2% chose to receive one. Those offered a prosthesis were significantly younger (P < 0.001), with a median age of 33 vs 37 years. There was no significant difference between the groups for LOS (P = 0.387), hospital re-admission rates (P = 0.539) or return to theatre rate (P = 0.999). In all, 33/885 patients were readmitted ≤30 days of orchidectomy, with one of 236 prosthesis patients requiring prosthesis removal (0.4%). Older age at orchidectomy was associated with an increased risk of 30-day hospital re-admission (odds ratio 1.032, P = 0.016). CONCLUSIONS: Concurrent insertion of a testicular prosthesis does not increase the complication rate of radical orchidectomy as determined by LOS, re-admission or the need for further surgery. Prosthesis insertion at the time of orchidectomy for testis cancer is safe and concerns about increased complications should not constrain the offer of testicular prosthesis insertion concurrently with primary surgery.

Dynamic sentinel lymph node biopsy for penile cancer: a comparison between 1- and 2-day protocols.

OBJECTIVE: To determine the outcome of clinically negative node (cN0) patients with penile cancer undergoing dynamic sentinel node biopsy (DSNB), comparing the results of a 1- and 2-day protocol that can be used as a minimal invasive procedure for staging of penile cancer. PATIENTS AND METHODS: This is a retrospective analysis of 151 cN0 patients who underwent DSNB from 2008 to 2013 for newly diagnosed penile cancer. Data were analysed per groin and separated into groups according to the protocol followed. The comparison of the two protocols involved the number of nodes excised, γ-counts, false-negative rates (FNR), and complication rates (Clavien-Dindo grading system). RESULTS: In all, 280 groins from 151 patients underwent DSNB after a negative ultrasound ± fine-needle aspiration cytology. The 1-day protocol was performed in 65 groins and the 2-day protocol in 215. Statistically significantly more nodes were harvested with the 1-day protocol (1.92/groin) compared with the 2-day protocol (1.60/groin). The FNRs were 0%, 6.8% and 5.1%, for the 1-day protocol, 2-day protocol, and overall, respectively. Morbidity of the DSNB was 21.4% for all groins, and 26.2% and 20.1% for the 1-day and 2-day protocols, respectively. Most of the complications were of Clavien-Dindo Grade 1-2. CONCLUSIONS: DSNB is safe for staging patients with penile cancer. There is a trend towards a 1-day protocol having a lower FNR than a 2-day protocol, albeit at the expense of a slightly higher complication rate.

Reactive oxygen species accelerate degradation of anion exchange membranes based on polyphenylene oxide in alkaline environments.

Anion exchange membranes (AEM) based on polyphenylene oxide (PPO) suffered quaternary-ammonium-cation-site degradation in alkaline environments. Surprisingly, the degradation rate was considerably faster in the presence of molecular oxygen. We postulated that the AEM cation-site catalyzes the reduction of dioxygen by hydroxide ions to yield the superoxide anion radical and the highly reactive hydroxyl free radical. We substantiated our hypothesis by using a phosphorous-containing spin trap (5-diisopropoxy-phosphoryl-5-methyl-1-pyrroline-N-oxide) to detect the adducts for both free radicals in situ using (31)P-NMR spectroscopy.