Extracellular Kir2.1C122Y Mutant Upsets Kir2.1-PIP2 Bonds and Is Arrhythmogenic in Andersen-Tawil Syndrome.

BACKGROUND: Andersen-Tawil syndrome type 1 is a rare heritable disease caused by mutations in the gene coding the strong inwardly rectifying K+ channel Kir2.1. The extracellular Cys (cysteine)122-to-Cys154 disulfide bond in the channel structure is crucial for proper folding but has not been associated with correct channel function at the membrane. We evaluated whether a human mutation at the Cys122-to-Cys154 disulfide bridge leads to Kir2.1 channel dysfunction and arrhythmias by reorganizing the overall Kir2.1 channel structure and destabilizing its open state. METHODS: We identified a Kir2.1 loss-of-function mutation (c.366 A>T; p.Cys122Tyr) in an ATS1 family. To investigate its pathophysiological implications, we generated an AAV9-mediated cardiac-specific mouse model expressing the Kir2.1C122Y variant. We employed a multidisciplinary approach, integrating patch clamping and intracardiac stimulation, molecular biology techniques, molecular dynamics, and bioluminescence resonance energy transfer experiments. RESULTS: Kir2.1C122Y mice recapitulated the ECG features of ATS1 independently of sex, including corrected QT prolongation, conduction defects, and increased arrhythmia susceptibility. Isolated Kir2.1C122Y cardiomyocytes showed significantly reduced inwardly rectifier K+ (IK1) and inward Na+ (INa) current densities independently of normal trafficking. Molecular dynamics predicted that the C122Y mutation provoked a conformational change over the 2000-ns simulation, characterized by a greater loss of hydrogen bonds between Kir2.1 and phosphatidylinositol 4,5-bisphosphate than wild type (WT). Therefore, the phosphatidylinositol 4,5-bisphosphate-binding pocket was destabilized, resulting in a lower conductance state compared with WT. Accordingly, on inside-out patch clamping, the C122Y mutation significantly blunted Kir2.1 sensitivity to increasing phosphatidylinositol 4,5-bisphosphate concentrations. In addition, the Kir2.1C122Y mutation resulted in channelosome degradation, demonstrating temporal instability of both Kir2.1 and NaV1.5 proteins. CONCLUSIONS: The extracellular Cys122-to-Cys154 disulfide bond in the tridimensional Kir2.1 channel structure is essential for the channel function. We demonstrate that breaking disulfide bonds in the extracellular domain disrupts phosphatidylinositol 4,5-bisphosphate-dependent regulation, leading to channel dysfunction and defects in Kir2.1 energetic stability. The mutation also alters functional expression of the NaV1.5 channel and ultimately leads to conduction disturbances and life-threatening arrhythmia characteristic of Andersen-Tawil syndrome type 1.

Current and Emerging Pharmacological Targets and Treatments of Urinary Incontinence and Related Disorders.

Overactive bladder syndrome with and without urinary incontinence and related conditions, signs, and disorders such as detrusor overactivity, neurogenic lower urinary tract dysfunction, underactive bladder, stress urinary incontinence, and nocturia are common in the general population and have a major impact on the quality of life of the affected patients and their partners. Based on the deliberations of the subcommittee on pharmacological treatments of the 7th International Consultation on Incontinence, we present a comprehensive review of established drug targets in the treatment of overactive bladder syndrome and the aforementioned related conditions and the approved drugs used in its treatment. Investigational drug targets and compounds are also reviewed. We conclude that, despite a range of available medical treatment options, a considerable medical need continues to exist. This is largely because the existing treatments are symptomatic and have limited efficacy and/or tolerability, which leads to poor long-term adherence. SIGNIFICANCE STATEMENT: Urinary incontinence and related disorders are prevalent in the general population. While many treatments have been approved, few patients stay on long-term treatment despite none of them being curative. This paper provides a comprehensive discussion of existing and emerging treatment options for various types of incontinence and related disorders.

Early in life stressful events induce chronic visceral pain and changes in bladder function in adult female mice through a mechanism involving TRPV1 and alpha 1A adrenoceptors.

BACKGROUND: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic pain disorder with multiple phenotypes, one of which is associated with an overactive adrenergic system. OBJECTIVE: We investigated if the maternal deprivation model (MDM) in female and male mice mimics IC/BPS phenotype and if the overstimulation of alpha 1A adrenoceptor (A1AAR) and the crosstalk with transient receptor potential vanilloid-1 (TRPV1) are involved in the generation of pain and bladder functional changes. DESIGN, SETTING, AND PARTICIPANTS: C57BL/6 female and male mice were submitted to MDM. TRPV1 knockout (KO) mice were used to study TRPV1 involvement. Silodosin administration to MDM mice was used to study A1AAR involvement. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was chronic visceral pain measured by Von Frey filaments analysis (effect size: 3 for wild type, 3.9 for TRPV1 KO). Bladder changes were secondary outcome measurements. Unpaired T test, Mann-Whitney test, one-way analysis of variance followed by Newman-Keuls multiple comparisons test, and Kruskal-Wallis followed by Dunn's multiple comparisons test were used where appropriate. RESULTS AND LIMITATIONS: MDM induces pain behavior in female and not in male mice. Bladder afferents seem sensitize as MDM also increase the number of small volume spots voided, the bladder reflex activity, and urothelial damage. These changes were similarly absent after A1AAR blockade with silodosin or by TRPV1 gene KO. The main limitation is the number/type of pain tests used. CONCLUSIONS: MDM induced in female mice is able to mimic IC/BPS phenotype, through mechanisms involving A1AAR and TRPV1. Therefore, the modulation of both receptors may represent a therapeutic approach to treat IC/BPS patients.

The urinary and prostatic microbiome in non-neurogenic male LUTS/BPH: A systematic review.

INTRODUCTION: Despite advancements in the treatment of benign prostatic hyperplasia (BPH), the mechanisms underlying BPH development and progression remain elusive and lacks a one-size-fits-all therapeutic solution. Prostatic inflammation contributes to BPH and lower urinary tract symptoms (LUTS), but the initial trigger remains unknown. Current research suggests dysbiosis of the urinary microbiome as a potential culprit. This systematic review explores the emerging field of the male urinary and prostatic microbiome and its relationship with BPH/LUTS. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. A systematic search in the Pubmed and Scopus databases was performed using specific terms. Inclusion criteria considered male non-neurogenic patients with LUTS due to BPH with analyses of urinary microbiome, concerning evaluation of English-language publications with relevance. RESULTS: Among seven articles involving 542 patients, there was an association between male LUTS/BPH and the urinary microbiome. Findings indicate a correlation between urinary microbiome dysbiosis and LUTS severity, with specific bacterial genera such as Streptococcus and Haemophilus linked to higher International Prostate Symptom Score (IPSS) scores and PSA levels. The fecal microbiome may be associated with LUTS, although contradictory findings are reported. The review also highlights methodological inconsistencies, small sample sizes, few negative controls and a lack of comprehensive clinical data as major limitations. CONCLUSIONS: While there is an undeniable correlation between the microbiome and LUTS/BPH, future research should aim to standardize sampling techniques and expand the score to include functional microbiome characterization, potentially leading to novel, microbiome-targeted therapeutic strategies for BPH.

Strategies for knowledge mobilization by advanced practice nurses in three hospitals in Spain: a qualitative study.

BACKGROUND: Evidence-based practice, in conjunction with optimum care quality, improves patients' clinical outcomes. However, its implementation in daily clinical practice continues to present difficulties. The aim of this study was to identify the strategies applied by Advanced Practice Nurses (APNs) to foster adherence to clinical practice guideline recommendations. METHODS: An exploratory qualitative study was conducted with six focus groups at three public hospitals belonging to the Balearic Islands Health Care Service (Spain). The study participants were 32 ward nurses and 5 advanced practice nurses working routinely with inpatients at these hospitals. The study was conducted from November 2020 to January 2021, using thematic analysis, based on the COREQ checklist. RESULTS: Four major themes related to the facilitation process were identified either by RNs and APNs: the context of the project, APN contribution to nursing team management, healthcare provision on the ward, and the acquisition and application of knowledge. CONCLUSIONS: The APNs adapted their actions to the characteristics and needs of the local context, employing strategies aimed at improving teamwork, healthcare, and knowledge management. Each of these contributions enhanced the sustainability of the changes made.

Self-reported urinary incontinence in women is higher with increased age, lower educational level, lower income, number of comorbidities, and impairment of mental health. Results of a large, population-based, national survey in Portugal.

PURPOSE: Urinary incontinence (UI) is a common condition in women. The aim of this study is to analyze women with self-reported UI, focusing on socio-demographic data, health-related conditions and comorbidities, and their impact on healthcare resources. METHODS: We analyzed data from a population-based survey with a representative sample of Portuguese women aged ≥ 18 years (n = 10,465). Women with self-reported symptoms of UI were distributed according to age, education level, and household income. The comparison of comorbidities and use of healthcare resources between the UI and non-UI groups was adjusted for age, education, and body mass index. We computed weighted prevalence and adjusted prevalence ratios with 95% confidence intervals using Poisson regression. RESULTS: Female UI prevalence was 9.9%, increasing with age (6.3% for 18- to 39-year-old, 40.8% for 75- to 85-year-old women). The prevalence decreased with education level (36.8% in women with no education, 4.6% in women with more than 12 years of education) and household income (29.8% in the 2nd quintile of income, 9.9% in the 5th quintile). Women with UI had a higher level of comorbidities, especially cardiovascular, respiratory, and mental health disorders. UI was also associated with higher consumption of healthcare resources. CONCLUSION: UI is highly prevalent among Portuguese women. It increases with age, low education level, and low household income. The use of healthcare resources was higher, possibly related with associated comorbidities. Though obtained in a single European country, these data may be useful to design a comprehensive management of UI in other parts of the western world.

Beyond the urothelium: Interplay between autonomic nervous system and bladder inflammation in urinary tract infection, bladder pain syndrome with interstitial cystitis and neurogenic lower urinary tract dysfunction in spinal cord injury-ICI-RS 2023.

INTRODUCTION: Inflammation and neuronal hypersensitivity are reactive protective mechanisms after urothelial injury. In lower urinary tract dysfunctions (LUTD), such as urinary tract infection (UTI), bladder pain syndrome with interstitial cystitis (BPS/IC) and neurogenic LUTD after spinal cord injury (SCI), chronic inflammation can develop. It is unclear how the protective reactionary inflammation escalates into chronic disease in some patients. METHODS: During its 2023 meeting in Bristol, the International Consultation on Incontinence-Research Society (ICI-RS) reviewed the urothelial and inflammatory changes after UTI, BPS/IC and SCI. Potential factors contributing to the evolution into chronic disease were explored in a think-tank. RESULTS: Five topics were discussed. (1) Visceral fat metabolism participates in the systemic pro-inflammatory effect of noradrenalin in BPS/IC and SCI. Sympathetic nervous system-adipocyte-bladder crosstalk needs further investigation. (2) Sympathetic hyperactivity also potentiates immune depression in SCI and needs to be investigated in BPS/IC. Gabapentin and tumor necrosis factor-α are promising research targets. (3) The exact peripheral neurons involved in the integrative protective unit formed by nervous and immune systems need to be further identified. (4) Neurotransmitter changes in SCI and BPS/IC: Neurotransmitter crosstalk needs to be considered in identifying new therapeutic targets. (5) The change from eubiosis to dysbiosis in SCI can contribute to UTI susceptibility and needs to be unraveled. CONCLUSIONS: The think-tank discussed whether visceral fat metabolism, immune depression through sympathetic hyperactivity, peripheral nerves and neurotransmitter crosstalk, and the change in microbiome could provide explanations in the heterogenic development of chronic inflammation in LUTD. High-priority research questions were identified.

Hydroclimate changes across the Amazon lowlands over the past 45,000 years.

Reconstructing the history of tropical hydroclimates has been difficult, particularly for the Amazon basin-one of Earth's major centres of deep atmospheric convection. For example, whether the Amazon basin was substantially drier or remained wet during glacial times has been controversial, largely because most study sites have been located on the periphery of the basin, and because interpretations can be complicated by sediment preservation, uncertainties in chronology, and topographical setting. Here we show that rainfall in the basin responds closely to changes in glacial boundary conditions in terms of temperature and atmospheric concentrations of carbon dioxide. Our results are based on a decadally resolved, uranium/thorium-dated, oxygen isotopic record for much of the past 45,000 years, obtained using speleothems from Paraíso Cave in eastern Amazonia; we interpret the record as being broadly related to precipitation. Relative to modern levels, precipitation in the region was about 58% during the Last Glacial Maximum (around 21,000 years ago) and 142% during the mid-Holocene epoch (about 6,000 years ago). We find that, as compared with cave records from the western edge of the lowlands, the Amazon was widely drier during the last glacial period, with much less recycling of water and probably reduced plant transpiration, although the rainforest persisted throughout this time.

Convective drying of mango stone for use as biomass.

Mango stone is an interesting biomass by-product with a considerable net calorific value. Mango production has significantly risen in the last few years, meaning that mango waste has increased as well. However, mango stone has a moisture content of about 60% (wet basis) and it is very important to dry the samples for using them in electrical and thermal energy production. In this paper, the main parameters involved in the mass transfer during drying are determined. Drying was carried out in a convective dryer through a set of experiments based on five drying air temperatures (100 °C, 125 °C, 150 °C, 175 °C and 200 °C) and three air velocities (1 m/s, 2 m/s and 3 m/s). Drying times ranged between 2 and 23 h. The drying rate was calculated from the Gaussian model whose values ranged from 1.5·10-6 to 6.3·10-4 s-1. Effective diffusivity was obtained as an overall parameter in the mass diffusion for each test. These values were found between 0.71·10-9 and 13.6·10-9 m2/s. The activation energy was calculated from the Arrhenius law for each test, made at different air velocities. These values were 36.7, 32.2 and 32.1 kJ/mol for 1, 2 and 3 m/s, respectively. This study provides information for future works on design, optimization and numerical simulation models in convective dryers for standard mango stone pieces according to industrial drying conditions.

Change detection versus change localization for faces, houses, and words.

Holistic processing aids in the discrimination of visually similar objects, but it may also come with a cost. Indeed holistic processing may improve the ability to detect changes to a face while impairing the ability to locate where the changes occur. We investigated the capacity to detect the occurrence of a change versus the capacity to detect the localization of a change for faces, houses, and words. Change detection was better than change localization for faces. Change localization outperformed change detection for houses. For words, there was no difference between detection and localization. We know from previous studies that words are processed holistically. However, being an object of visual expertise processed holistically, visual words are also a linguistic entity. Previously, the word composite effect was found for phonologically consistent words but not for phonologically inconsistent words. Being an object of visual expertise for which linguistic information is important, letter position information, is also crucial. Thus, the importance of localization of letters and features may augment the capacity to localize a change in words making the detection of a change and the detection of localization of a change equivalent.

The mechanisms supporting holistic perception of words and faces are not independent.

The question of whether word and face recognition rely on overlapping or dissociable neural and cognitive mechanisms received considerable attention in the literature. In the present work, we presented words (aligned or misaligned) superimposed on faces (aligned or misaligned) and tested the interference from the unattended stimulus category on holistic processing of the attended category. In Experiment 1, we found that holistic face processing is reduced when a face was overlaid with an unattended, aligned word (processed holistically). In Experiment 2, we found a similar reduction of holistic processing for words when a word was superimposed on an unattended, aligned face (processed holistically). This reciprocal interference effect indicates a trade-off in holistic processing of the two stimuli, consistent with the idea that word and face recognition may rely on non-independent, overlapping mechanisms.

Timing and structure of the Younger Dryas event and its underlying climate dynamics.

The Younger Dryas (YD), arguably the most widely studied millennial-scale extreme climate event, was characterized by diverse hydroclimate shifts globally and severe cooling at high northern latitudes that abruptly punctuated the warming trend from the last glacial to the present interglacial. To date, a precise understanding of its trigger, propagation, and termination remains elusive. Here, we present speleothem oxygen-isotope data that, in concert with other proxy records, allow us to quantify the timing of the YD onset and termination at an unprecedented subcentennial temporal precision across the North Atlantic, Asian Monsoon-Westerlies, and South American Monsoon regions. Our analysis suggests that the onsets of YD in the North Atlantic (12,870 ± 30 B.P.) and the Asian Monsoon-Westerlies region are essentially synchronous within a few decades and lead the onset in Antarctica, implying a north-to-south climate signal propagation via both atmospheric (decadal-time scale) and oceanic (centennial-time scale) processes, similar to the Dansgaard-Oeschger events during the last glacial period. In contrast, the YD termination may have started first in Antarctica at ∼11,900 B.P., or perhaps even earlier in the western tropical Pacific, followed by the North Atlantic between ∼11,700 ± 40 and 11,610 ± 40 B.P. These observations suggest that the initial YD termination might have originated in the Southern Hemisphere and/or the tropical Pacific, indicating a Southern Hemisphere/tropics to North Atlantic-Asian Monsoon-Westerlies directionality of climatic recovery.

Towards a Broad-Persistent Advising Approach for Deep Interactive Reinforcement Learning in Robotic Environments.

Deep Reinforcement Learning (DeepRL) methods have been widely used in robotics to learn about the environment and acquire behaviours autonomously. Deep Interactive Reinforcement 2 Learning (DeepIRL) includes interactive feedback from an external trainer or expert giving advice to help learners choose actions to speed up the learning process. However, current research has been limited to interactions that offer actionable advice to only the current state of the agent. Additionally, the information is discarded by the agent after a single use, which causes a duplicate process at the same state for a revisit. In this paper, we present Broad-Persistent Advising (BPA), an approach that retains and reuses the processed information. It not only helps trainers give more general advice relevant to similar states instead of only the current state, but also allows the agent to speed up the learning process. We tested the proposed approach in two continuous robotic scenarios, namely a cart pole balancing task and a simulated robot navigation task. The results demonstrated that the agent's learning speed increased, as evidenced by the rising reward points of up to 37%, while maintaining the number of interactions required for the trainer, in comparison to the DeepIRL approach.

Assessing the energy recovery potential at district metered areas inlets of water supply systems: A Spanish case study.

The energy required for various processes in the water cycle can have significant economic and environmental impacts. Therefore, efficient energy management in urban water supply systems is crucial for a sustainable operation. By installing energy recovery technologies in these facilities, it is possible to reap the benefits of the infrastructure design by saving energy. In this study, a new methodology to assess the energy recovery at the inlets of district metered areas is presented, considering the city of Murcia (Spain) as case study. This methodology is based on creating a detailed model of city water supply system and calibrating such model with an experimental campaign of measurements. Then, the assessment of the hydraulic potential recovery is analysed through two different energy estimators, one considering the minimum available net head and the other assuming a variable net head. Results show that there are several points where turbines could be installed, most of them recovering in between 1000-5000 kWh, which could be used to cover the yearly energy consumption of about 24-120 m2 of a school or 10-50 traffic lights of such area. Moreover, in some points it could be recovered up to 14500 kWh. Even though these values are not high, the energy recovered could be used for self-consumption of nearby electrical loads, at the time that reduces the pressure in the system, thus leading to leak reductions. Moreover, this kind of energy recovery does not reduce the potential of other proposals for upstream energy recovery, such as replacing pressure reduction valves with turbines instead. The scripts developed to apply the proposed methodology are available in EPANET-Octave file exchange for the researcher community.

Partial overlap between holistic processing of words and Gestalt line stimuli at an early perceptual stage.

A dual-route account of holistic processing has been proposed, which includes a stimulus-based and experience-based approach to holistic processing. The bottom-up route was suggested by the observation of holistic processing for novel Gestalt line patterns in the absence of expertise. For words, there is mainly evidence for a late, lexical, experience-based locus of holistic processing with scarce evidence for an early, stimulus-based locus. However, salient early Gestalt information (i.e., connectedness, closure, and continuity between parts) are important for letter and word identification. Thus, there might be an overlap at an early, perceptual processing stage, between Gestalt stimulus-based holistic processing and word holistic processing. In the task we used, words and Gestalt line patterns were superimposed, and we evaluated whether one class of stimuli was processed less holistically when an aligned other class pattern (processed holistically) was superimposed. There was some evidence supporting an early locus for the influence of word processing on Gestalt line patterns, but the interaction between the two stimuli was not reciprocal, which needs further clarification. When an aligned word (processed holistically) was overlaid on a line pattern, the line pattern was processed less holistically. However, when an aligned line pattern (processed holistically) was overlaid on a word, the word was not processed less holistically. This pattern might result from the higher cohesiveness of words and their automaticity and feedback from the lexicon.

Event-Based Angular Speed Measurement and Movement Monitoring.

Computer vision techniques can monitor the rotational speed of rotating equipment or machines to understand their working conditions and prevent failures. Such techniques are highly precise, contactless, and potentially suitable for applications without massive setup changes. However, traditional vision sensors collect a significant amount of data to process and measure the rotation of high-speed systems, and they are susceptible to motion blur. This work proposes a new method for measuring rotational speed processing event-based data applied to high-speed systems using a neuromorphic sensor. This sensor produces event-based data and is designed to work with high temporal resolution and high dynamic range. The main advantages of the Event-based Angular Speed Measurement (EB-ASM) method are the high dynamic range, the absence of motion blurring, and the possibility of measuring multiple rotations simultaneously with a single device. The proposed method uses the time difference between spikes in a Kernel or Window selected in the sensor frame range. It is evaluated in two experimental scenarios by measuring a fan rotational speed and a Router Computer Numerical Control (CNC) spindle. The results compare measurements with a calibrated digital photo-tachometer. Based on the performed tests, the EB-ASM can measure the rotational speed with a mean absolute error of less than 0.2% for both scenarios.

Impact of advanced practice nurses in hospital units on compliance with clinical practice guidelines: a quasi-experimental study.

BACKGROUND: Incorporating the best available evidence into clinical practice is a determining challenge for healthcare professionals and organisations. The role of advanced practice nurses is viewed as a facilitator to adapt guideline recommendations to suit specific contexts and to overcome barriers to implementation. In this study, we evaluate the impact of advanced practice nurses on clinical indicators of hospitalised patients and on adherence to recommendations derived from two clinical practice guidelines (pressure ulcer prevention and treatment and vascular access device management). METHODS: Quasi-experimental study in five intervention (IU) and five control (CU) hospital units at three hospitals in Spain (period 2018-19). Five advanced practice nurses were incorporated into IU, with the intention that would produce attitudinal changes and enhance the skills and knowledge of the nursing team regarding 18 clinical practice recommendations. In this study, 41 indicators were evaluated through direct observation of all patients admitted, at monthly intervals for 1 year. Outcomes were assessed by means of a descriptive, multi-line regression and association analysis. RESULTS: The study population was composed of 3742 inpatients admitted for pressure ulcer assessment and 2631 fitted with vascular access devices. By the end of the study period, all variables had improved in the IU, where average compliance with recommendations was statistically significantly higher (pressure ulcer guidance 7.9 ± 1.9 vs 6.0 ± 1.7. OR 1.86, 95% CI 1.67-2.05; vascular access devices guidance 5.4 ± 1.4 vs 4.4 ± 1,6. OR 1.06, 95% CI 0.95-1.17). The prevalence of pressure lesions and catheter-related adverse events decreased statistically significantly in the IU compared to the CU. The prevalence of pressure ulcers decreases (5.7% in IU vs 8.7% in CU p < 0.005) as well as the prevalence of adverse events related to the catheter (14% In IU vs 21.6% in CU p < 0.005). The unnecessary catheters decressed in IU 10.9% VS CU 15.8% (p < 0.005). CONCLUSIONS: The incorporation of an advanced practice nurse statistically significantly improves clinical indicators related to the prevention and treatment of pressure ulcers and to the management of vascular access devices. TRIAL REGISTRATION: ISRCTN18259923 retrospectively registered on 11/02/2022.

Palladium-Catalyzed Aminocyclization-Coupling Cascades: Preparation of Dehydrotryptophan Derivatives and Computational Study.

Dehydrotryptophan derivatives have been prepared by palladium-catalyzed aminocyclization-Heck-type coupling cascades starting from o-alkynylaniline derivatives and methyl α-aminoacrylate. Aryl, alkyl (primary, secondary, and tertiary), and alkenyl substituents have been introduced at the indole C-2 position. Further variations at the indole benzene ring, as well as the C-2-unsubstituted case, have all been demonstrated. In the case of C-2 aryl substitution, the preparation of the o-alkynylaniline substrate by Sonogashira coupling and the subsequent cyclization-coupling cascade have been performed in a one-pot protocol with a single catalyst. DFT calculations have revealed significant differences in the reaction profiles of these reactions relative to those involving methyl acrylate or methacrylate, and between the reactions of the free anilines and their corresponding carbamates. Those calculations suggest that the nature of the alkene and of the acid HX released in the HX/alkene exchange step that precedes C-C bond formation could be responsible for the experimentally observed differences in reaction efficiencies.

Artificial urinary sphincter or a second adjustable transobturator male system offer equivalent outcomes in patients whom required revision on the initial ATOMS device: An international multi-institutional experience.

AIM: To evaluate treatment options after surgical revision of adjustable transobturator male system (ATOMS) and the results of further incontinence implantation. MATERIALS AND METHODS: A retrospective multicenter study evaluating patients with surgical revision of ATOMS in academic institutions. Causes and factors affecting revision-free interval were studied and also the frequency of device explant and placement of second ATOMS or artificial urinary sphincter (AUS) at surgeon discretion. Operative results, complications (Clavien-Dindo), and efficacy (postoperative pad-test, pad-count, patient satisfaction, and patient global impression of improvement [PGI-I scale]) of each treatment option were compared. RESULTS: Seventy-eight out of 902 patients (8.65%) with ATOMS underwent surgical revision at 4.1 ± 2.4 years mean follow-up and 75 (8.3%) were explanted. The main causes for revision included persistence of incontinence (35.9%) and scrotal port erosion (34.6%). Independent risk factors of the shortened revision-free interval were previous anti-incontinence surgery (HR, 1.83; 95% CI, 1.06-3.16; p = 0.007) and port erosion (HR, 1.83; 95% CI, 1.06-3.16; p = 0.0027). Fifty-eight (6.4%) received a second implant: 31 repeated ATOMS and 27 AUS. Operative time was longer for AUS (p = .003). The visual analog scale of pain at hospital discharge (p = 0.837) and postoperative complications (p = 0.154) were equivalent. The predominant cuff size for AUS was 4.5 cm (59.3%). Mean follow-up after the second implant was 29.1 ± 25.8 months. Postoperative efficacy of secondary treatment results favored ATOMS based on pad-test (p = 0.016), pad-count (p = 0.029), patient satisfaction (p = 0.04), and PGI-I (p = 0.025). CONCLUSIONS: ATOMS surgical revision due to different reasons generally leads to device explant. Rescue treatment is possible with ATOMS or AUS. No difference in postoperative complications was detected between secondary devices, but efficacy favors repeating ATOMS implantation.

Mini-Slings: Do They Stand the Test of Time? A 10-Year Cohort.

INTRODUCTION: It is known that failures after midurethral slings increase with the follow-up time. Nevertheless, data concerning mini-slings are sparse. To clarify this statement, we analyze a mini-sling cohort with a median follow-up of 10 years. Although the brand used, MiniArc®, is no longer available, an identical device, Solyx™, can still be used, which makes the analysis of the cohort clinically relevant. MATERIAL AND METHODS: A total of 172 women with predominant stress urinary incontinence (SUI) were consecutively treated with the mini-sling MiniArc® from 2006 until 2013. They were reevaluated in 2018. The primary outcome, treatment success, was defined as no self-reported SUI symptoms and no reintervention. Secondary outcomes included the response to patient-reported outcomes. Adverse events were assessed. RESULTS: After a median follow-up time of 113 months, 115 (66.9%) women were available for reevaluation. Forty-four (38.3%) women self-reported SUI. Seventeen women had been reoperated, 14 (12.2%) due to the reappearance of SUI and 3 due to complications. Altogether, MiniArc® had an overall success rate of 47.0% at 10 years. Among those not reoperated, 63.3% stated that they were much better or very much better in Patient Global Impression of Improvement (PGI-I) and 71.4% affirmed that their continence problem was normal or mild in Patient Global Impression of Severity (PGI-S). Almost 85% would repeat the surgery. Reoperation due to complications was rare (2.6%). De novo urgency appeared in 30.6% of the patients and it was managed with anticholinergic drugs with favorable outcomes. DISCUSSION/CONCLUSION: This report adds evidence to the long-term outcomes of mini-slings, confirming that they can cure or improve SUI and give patients high satisfaction rates, at the expense of low morbidity.