Efficacy and safety of Optilume® Paclitaxel-coated urethral dilatation balloon in real-life: Experience in a Spanish Multicenter Study.

INTRODUCTION: The Optilume® Paclitaxel-coated urethral dilatation balloon is an alternative to conventional endoscopic treatments that combines mechanical dilatation with local delivery of paclitaxel. OBJECTIVE: To describe the success rate and analyze the safety of the device in real clinical practice. To evaluate possible predictors of treatment failure. MATERIALS AND METHODS: Retrospective multicenter study in patients diagnosed with urethral stricture and treated with an Optilume® balloon in routine clinical practice. Data were collected from flowmetry, questionnaires (PROM and IPSS) and cystoscopy before surgery, and 3, 6 and 12 months after the procedure, according to standard practice. Surgical success was defined as the absence of subsequent urethral manipulation and a Qmax > 10 ml/s. RESULTS: 238 patients treated with Optilume® in 12 Spanish hospitals between May 2021 and April 2024 were included in the study. Of these, 156 who had a minimum follow-up of 3 months, were analyzed. Median stricture length: 1.5 cm (0.5 - 5.3), mainly in bulbar urethra (87.7%). Of the total, 12.8% of patients had a history of pelvic radiotherapy, and 81.4% had undergone prior urethral manipulation. Postoperative complications were reported in 14.2% of the total. The treatment success rate was 73.8%, with a median follow-up of 8 months (5-12). No predictors of stricture recurrence were identified. Recurrence rates were higher in strictures located in the posterior versus anterior urethra (42.9% vs. 24.6%, p = 0.126). No significant differences were observed between patients with and without prior urethral manipulation. CONCLUSION: Treatment with Optilume® has been shown to be safe and effective in short-term routine clinical practice.

Hypoglycemia in Critically Ill Patients: A Concise Clinical Review.

Hypoglycemia in critical care is a well-documented phenomenon, linking both physiological and clinical evidence to harmful outcomes and an increased risk of mortality. Its implications span medical and non-medical consequences, such as cardiovascular and cerebrovascular complications, and escalated health care expenses and hospitalization duration. Mitigation measures for modifiable risk factors and education for both patients and health care providers on hypoglycemia can effectively prevent the onset of inpatient hypoglycemia. This concise clinical review offers a brief overview of hypoglycemia in critically ill patients, encompassing its pathophysiology, etiology, diagnosis, management, and prevention.

Wavy Graphene Nanoribbons Containing Periodic Eight-Membered Rings for Light-Emitting Electrochemical Cells.

Precision graphene nanoribbons (GNRs) offer distinctive physicochemical properties that are highly dependent on their geometric topologies, thereby holding great potential for applications in carbon-based optoelectronics and spintronics. While the edge structure and width control has been a popular strategy for engineering the optoelectronic properties of GNRs, non-hexagonal-ring-containing GNRs remain underexplored due to synthetic challenges, despite offering an equally high potential for tailored properties. Herein, we report the synthesis of a wavy GNR (wGNR) by embedding periodic eight-membered rings into its carbon skeleton, which is achieved by the A2B2-type Diels-Alder polymerization between dibenzocyclooctadiyne (6) and dicyclopenta[e,l]pyrene-5,11-dione derivative (8), followed by a selective Scholl reaction of the obtained ladder-type polymer (LTP) precursor. The obtained wGNR, with a length of up to 30 nm, has been thoroughly characterized by solid-state NMR, FT-IR, Raman, and UV/Vis spectroscopy with the support of DFT calculations. The non-planar geometry of wGNR efficiently prevents the inter-ribbon π-π aggregation, leading to photoluminescence in solution. Consequently, the wGNR can function as an emissive layer for organic light-emitting electrochemical cells (OLECs), offering a proof-of-concept exploration in implementing luminescent GNRs into optoelectronic devices. The fast-responding OLECs employing wGNR will pave the way for advancements in OLEC technology and other optoelectronic devices.

Bystander monocytic cells drive infection-independent NLRP3 inflammasome response to SARS-CoV-2.

The pathogenesis of COVID-19 is associated with a hyperinflammatory immune response. Monocytes and macrophages play a central role in this hyperinflammatory response to SARS-CoV-2. NLRP3 inflammasome activation has been observed in monocytes of patients with COVID-19, but the mechanism and consequences of inflammasome activation require further investigation. In this study, we inoculated a macrophage-like THP-1 cell line, primary differentiated human nasal epithelial cell (hNEC) cultures, and primary monocytes with SARS-CoV-2. We found that the activation of the NLRP3 inflammasome in macrophages does not rely on viral replication, receptor-mediated entry, or actin-dependent entry. SARS-CoV-2 productively infected hNEC cultures without triggering the production of inflammasome cytokines IL-18 and IL-1ß. Importantly, these cytokines did not inhibit viral replication in hNEC cultures. SARS-CoV-2 inoculation of primary monocytes led to inflammasome activation and induced a macrophage phenotype in these cells. Monocytic cells from bronchoalveolar lavage (BAL) fluid, but not from peripheral blood, of patients with COVID-19, showed evidence of inflammasome activation, expressed the proinflammatory marker CD11b, and displayed oxidative burst. These findings highlight the central role of activated macrophages, as a result of direct viral sensing, in COVID-19 and support the inhibition of IL-1ß and IL-18 as potential therapeutic strategies to reduce immunopathology without increasing viral replication. IMPORTANCE: Inflammasome activation is associated with severe COVID-19. The impact of inflammasome activation on viral replication and mechanistic details of this activation are not clarified. This study advances our understanding of the role of inflammasome activation in macrophages by identifying TLR2, NLRP3, ASC, and caspase-1 as dependent factors in this activation. Further, it highlights that SARS-CoV-2 inflammasome activation is not a feature of nasal epithelial cells but rather activation of bystander macrophages in the airway. Finally, we demonstrate that two pro inflammatory cytokines produced by inflammasome activation, IL-18 and IL-1ß, do not restrict viral replication and are potential targets to ameliorate pathological inflammation in severe COVID-19.

Modeling Photodissociation: Quantum Dynamics Simulations of Methanol.

A comprehensive computational study of the gas-phase photodissociation dynamics of methanol is presented. Using a multiconfigurational active space based method (RASSCF) to obtain multidimensional potential energy surfaces (PESs) on-the-fly, direct quantum dynamics simulations were run using the variational multi-configurational Gaussian method (DD-vMCG). Different initial excitation energies were simulated to investigate the dependence of the branching ratios on the electronic state being populated. A detailed mechanistic explanation is provided for the observed differences with respect to the excitation energy. Population of the lowest lying excited state of methanol leads to rapid hydroxyl hydrogen loss as the main dissociation channel. This is rationalized by the strongly dissociative nature of the PES cut along the O-H stretching coordinate, confirmed by the broad feature in the absorption spectrum. In contrast, more energetic excitations lead mainly to C-O bond breaking. Again, analysis of the diabatic surfaces offers a clear explanation in terms of the nature of the electronic states involved and the coupling between them. The type of calculations presented, as well as the subsequent analysis of the results, should be seen as a general workflow for the modeling of photochemical reactions.

Acoustic Communication in Dendroctonus adjunctus Blandford (Curculionidae Scolytinae): Description of Calls and Sound Production Mechanism.

The acoustic communication system (ACS) in bark beetles has been studied mainly in species of the genera Dendroctonus, Ips and Polygraphus. Specifically, ACS of the roundheaded pine beetle, Dendroctonus adjunctus, has been little studied. In this study, we described the stridulatory apparatus of this beetle using optical and scanning electron microscopy and recorded the call types produced by males in three behavioral contexts: stress, female-male-, and male-male interactions. From the spectrograms and waveforms, call types, as well as temporal (tooth strike, tooth strike rate, and intertooth strike interval) and spectral features (minimum, maximum and dominant frequency), were determined. Males have a functional elytro-tergal stridulatory apparatus-females do not-consisting of a file for the pars stridens and two lobes for the plectrum. Most of spectro-temporal features were statistically different between single- and multi-noted calls and across the three behavioral contexts. In the male-male interaction, a new type of call named "withdrawal" was produced by the male withdrawing or fleeing. Our results suggest that the spectro-temporal features of single- and multiple-noted calls in the three behavioral conditions are specific and different from each other. Yet, the combination of single and multiple calls determines an overall calling pattern characteristic of the tested behaviors and, therefore, is species-specific.

From Chalcogen Bonding to S-π Interactions in Hybrid Perovskite Photovoltaics.

The stability of hybrid organic-inorganic halide perovskite semiconductors remains a significant obstacle to their application in photovoltaics. To this end, the use of low-dimensional (LD) perovskites, which incorporate hydrophobic organic moieties, provides an effective strategy to improve their stability, yet often at the expense of their performance. To address this limitation, supramolecular engineering of noncovalent interactions between organic and inorganic components has shown potential by relying on hydrogen bonding and conventional van der Waals interactions. Here, the capacity to access novel LD perovskite structures that uniquely assemble through unorthodox S-mediated interactions is explored by incorporating benzothiadiazole-based moieties. The formation of S-mediated LD structures is demonstrated, including one-dimensional (1D) and layered two-dimensional (2D) perovskite phases assembled via chalcogen bonding and S-π interactions. This involved a combination of techniques, such as single crystal and thin film X-ray diffraction, as well as solid-state NMR spectroscopy, complemented by molecular dynamics simulations, density functional theory calculations, and optoelectronic characterization, revealing superior conductivities of S-mediated LD perovskites. The resulting materials are applied in n-i-p and p-i-n perovskite solar cells, demonstrating enhancements in performance and operational stability that reveal a versatile supramolecular strategy in photovoltaics.

Selective treatment of clinical mastitis: Assessment of the Net Cash Impact on Dairy Farms Under Diverse Scenarios. A European Perspective.

Selective treatment of clinical mastitis (STCM) potentially reduces antimicrobial use without negative implications on cow's milk production or health. However, this approach comes with additional costs. The aim of this study was to evaluate the net cash impact (NCI) of implementing STCM compared with blanket treatment of clinical mastitis (BTCM) under different diagnostic-test turnaround times (24 h, 14 h, and 8 h) using a stochastic partial budget analysis with Monte Carlo simulation. The target population was European commercial dairy herds; therefore, the model inputs were primarily from European sources. Additionally, variables associated with dairy management programs were obtained from USDA sources, worldwide multisite clinical trials, and expert opinion. The output was calculated by subtracting the cost of STCM from the cost of BTCM and it represented the expected NCI if a herd switched from BTCM to STCM. Depending on the time-to-treatment efficiency and diagnostic-test turnaround time, the expected mean NCI, assuming that STCM has no impact on the cow's future health or production, ranged from +€8.7 to +€12.4 per case with 72.4% to 84.8% of the iterations being ≥ €0. Moreover, using the numerically favorable health and production effects of STCM reported in the literature, the expected mean NCI ranged from +€44.5 to +€48.1 per case with 93.6% to 95.4% of the iterations being ≥ €0. The variables with the greatest contribution to NCI variance were proportion of gram-positive cases (39.2% of the variance) and days out of the tank for treated cows (22.0%). However, if future cow's health and production were accounted for, culling risk (24.6%), recurrence risk (19.4%), and milk yield (10.6%) would have the greatest contribution to NCI. The sensitivity analysis indicated that farms with high clinical mastitis incidence, low proportion of gram-positive cases, large number of days out of the tank for treated cows, higher milking frequency or using automatic milking systems, not using the highest priced diagnostic tests, and having high antimicrobial treatment costs are the best candidates for STCM. Improving time-to-treatment efficiency, for example, by using a rapid diagnostic test, leads to a favorable NCI, while high daily milk yield and milk price enhances the NCI in already positive scenarios. Finally, the cash flow entirely depends on future cow's health and milk yield. In conclusion, results indicate that overall, STCM is a practice that positively impacts the NCI of many herds.

Effectiveness of handheld near infrared spectrometer for traceability of Angus steaks.

The feasibility of Near Infrared Spectroscopy was assessed for aging traceability of steaks of Angus beef (Biceps femoris) individually vacuum-packaged, as well as for the prediction of the refrigeration storage time (0, 7, and 14 days). For this purpose, a total of 288 steaks homogeneously distributed among the sampling times were used. The model developed by Partial Least Squares-Discriminant Analysis offered high discrimination ability between aged beef vs. non-aged. The accuracy after external validation exceeded 90%. Regarding the predictive capacity of the storage time, it was greater on the set of aged samples, in which the accuracy achieved values higher than 96%, while the accuracy decreased to 75% for the non-aged samples. Results obtained support the ability of NIRS technology to be considered in any digital transformation strategy for traceability across the meat supply chain.

Relation of changes in peak expiratory flow (PEF) and forced expiratory volume in 1 s (FEV1) during bronchoconstriction.

Diagnosis of asthma can be confirmed based on variability in peak expiratory flow (PEF) or changes in forced expiratory volume in 1 s (FEV1) measured with spirometry. Our aim was to use methacholine challenge as a model of induced airway obstruction to assess how well relative changes in PEF reflect airway obstruction in comparison to relative changes in FEV1. We retrospectively studied 878 patients who completed a methacholine challenge test. To assess congruency along with differences between relative changes in FEV1 and PEF during airway obstruction, a regression analysis was performed, and a Bland & Altman plot was constructed. ROC analysis, sensitivity, specificity, positive and negative predictive values and κ-coefficient were used to analyze how decrease in PEF predicts decrease of 10% or 15% in FEV1. The relative change in PEF was on average less than the relative change in FEV1. In the ROC analysis areas under the curve were 0.844 and 0.893 for PEF decrease to predict a 10% and 15% decrease in FEV1, respectively. The agreement between changes in PEF and FEV1 varied from fair to moderate. Airway obstruction detected by change in PEF was false in about 40% of cases when compared to change in FEV1. Change in PEF is not a very accurate measure of airway obstruction when compared to change in FEV1. Replacing peak flow metre with a handheld spirometer might improve diagnostic accuracy of home monitoring in asthma.

Essential Review of Oncological Emergencies.

Innovations in oncology have expanded treatment eligibility, leading to a rise in cancer patients requiring critical care. This necessitates that all critical care clinicians possess a fundamental knowledge of prevalent oncological conditions and identify emergent scenarios requiring immediate action. This article will explore key oncological complications and their management approaches.

Deep mutational scanning of hepatitis B virus reveals a mechanism for cis-preferential reverse transcription.

Hepatitis B virus (HBV) is a small double-stranded DNA virus that chronically infects 296 million people. Over half of its compact genome encodes proteins in two overlapping reading frames, and during evolution, multiple selective pressures can act on shared nucleotides. This study combines an RNA-based HBV cell culture system with deep mutational scanning (DMS) to uncouple cis- and trans-acting sequence requirements in the HBV genome. The results support a leaky ribosome scanning model for polymerase translation, provide a fitness map of the HBV polymerase at single-nucleotide resolution, and identify conserved prolines adjacent to the HBV polymerase termination codon that stall ribosomes. Further experiments indicated that stalled ribosomes tether the nascent polymerase to its template RNA, ensuring cis-preferential RNA packaging and reverse transcription of the HBV genome.

Structure of the interleukin-5 receptor complex exemplifies the organizing principle of common beta cytokine signaling.

Cytokines regulate immune responses by binding to cell surface receptors, including the common subunit beta (ßc), which mediates signaling for GM-CSF, IL-3, and IL-5. Despite known roles in inflammation, the structural basis of IL-5 receptor activation remains unclear. We present the cryo-EM structure of the human IL-5 ternary receptor complex, revealing architectural principles for IL-5, GM-CSF, and IL-3. In mammalian cell culture, single-molecule imaging confirms hexameric IL-5 complex formation on cell surfaces. Engineered chimeric receptors show that IL-5 signaling, as well as IL-3 and GM-CSF, can occur through receptor heterodimerization, obviating the need for higher-order assemblies of ßc dimers. These findings provide insights into IL-5 and ßc receptor family signaling mechanisms, aiding in the development of therapies for diseases involving deranged ßc signaling.

Water level drawdown induces a legacy effect on the seed bank and retains sediment chemistry in a eutrophic clay wetland.

The lack of extreme water level fluctuations in managed, non-peat forming wetland ecosystems can result in decreased productivity through the loss of heterogeneity of these ecosystems. Stochastic disruption, such as a water level drawdown, can effectively reverse this effect and return the wetland to a more productive state, associated with higher biodiversity through new vegetation development. Yet, aside from the effect on vegetation dynamics, little is known about longer-term effects (30 years) of a water level drawdown, hereafter referred to as legacy effects, and how this may impact future water level drawdowns. Here, we aim to unravel the legacy effects of a water level drawdown, stand alone and along a water level gradient, on seed bank properties and nutrient availability in a eutrophic clay wetland. To identify these, we studied the hydrologically managed nature reserve Oostvaardersplassen in the Netherlands. Here, one section was subjected to a multi-year water level drawdown and another section was kept inundated. We determined seed bank properties in both areas, spatially and along a soil elevation gradient (20 cm). Nutrient availability was measured by taking sediment samples along the water level gradient and through experimental manipulation of the water level in an indoor mesocosm experiment. Germination was higher in locations with a water level drawdown history, especially at relatively high elevations. Additionally, the proportion of pioneer species in the seed bank was higher in the water level drawdown area. Overall, nutrient concentrations were higher compared to other aquatic systems. Nutrient availability was higher in the inundated area and did not respond to the water level gradient. We conclude that 30 years after an induced water level drawdown there is no depletion of nutrients, while we still observe a legacy effect in the number of viable seeds in the seed bank.

Mechanical Behaviour of As-Manufactured and Repaired Aligned Discontinuous Basalt Fibre-Reinforced Vitrimer Composites.

The aim of this research is to investigate basalt as a natural mineral-based fibre together with a vitrimeric resin as a sustainable alternative to standard composite materials. Vitrimers combine the properties of thermoset and thermoplastic polymers, enabling the repair of specimens and hence prolonging the lifetime of the composite material. The micro-mechanical characteristics between the basalt fibres and the vitrimer resin are reported and shown to match those of a standard Skyflex K51 epoxy resin. Discontinuous (4 mm) basalt fibres were employed to produce aligned discontinuous fibre-reinforced composites (ADFRCs) using the high-performance discontinuous fibre (HiPerDiF) technology. The mechanical characteristics of the laminates were investigated through tensile testing and the fracture zones were analysed under a scanning electron microscope. By normalising the results by their respective fibre volume fraction, it was discovered that the vitrimer-basalt ADFRCs exhibited, on average, a 4% higher strength and a 25% higher stiffness compared to their basalt epoxy counterparts. The repair potential of the vitrimer ADFRC specimens was explored during low-temperature compression repair. Two approaches were tested using double-sided local- and full-patch repair. Both successfully recovered a significant amount of their prime strength. In conclusion, the potential of the sustainable vitrimer-basalt composite is shown by its competitive mechanical performance. Combining this with the manufacturing flexibility, repair potential, and recyclability of the material, the vitrimer-basalt composite seems to be a competitive alternative to standard glass epoxies.

Ground penetrating radar at work: A realistic perspective on utility surveying in the Netherlands through a comprehensive ground-truth dataset.

This dataset provides a comprehensive compilation of Ground Penetrating Radar (GPR) surveys across 125 utility surveying activities in the Netherlands. The dataset details the specific use of GPR in each authentic real-life utility surveying activity, whether employed independently or as a complementary tool alongside existing surveying methods, with or without post-processing. The dataset includes 959 radargrams, ground-truth information obtained from trial trenches, and an inventory of construction, geophysical, infrastructural, and technical features. The GPR utilised in all activities is an air-coupled radar with a 500 MHz frequency antenna, a GNSS RTK positioning system, and a measuring wheel encoder. This ground-truth dataset provides researchers with a valuable resource to further assess the practical efficacy of GPR as a utility surveying method, refine radargram processing algorithms and techniques, and explore the possibilities of predictive modelling.

A Case Series of Patients With Complex Airway Disease and Large Thyroid Tumors Anterior to the Trachea Precluding Tracheostomy.

BACKGROUND: This case series explores the management of respiratory failure in patients with large anterior tracheal thyroid tumors where tracheostomy is not an option. To our knowledge, this study is the first to address the challenges associated with caring for such patients. CASE SUMMARY: We present the clinical courses of four intubated adults with advanced thyroid cancer and complex airway issues that preclude surgical tracheostomy. Interventions included custom airway stents, long-term intubation, and oncological therapies. Ethical quandaries around patient autonomy and capacity emerged, exacerbated by the absence of viable exit strategies for prolonged intubation, notably the performance of a tracheostomy, causing emotional distress in patients, families, and staff. CONCLUSIONS: This study showcases the multifaceted challenges in medical, ethical, and emotional domains associated with managing intubated patients with complex disease precluding tracheotomies. We advocate for a nuanced, multidisciplinary, and personalized approach to confront unique issues in airway management, ethical considerations, and disposition.

Elevated brain natriuretic peptide in a patient with metastatic cancer without heart failure: A case study.

ABSTRACT: Brain natriuretic peptide (BNP) is a well-established biomarker for heart failure (HF). However, its diagnostic utility can be limited in patients with comorbidities that independently elevate serum BNP levels, including chronic renal failure and sepsis. We describe a rare occurrence of significantly elevated serum BNP levels in a patient with metastatic urothelial cancer without HF or obvious signs of sepsis. The report highlights the need for considering alternative causes for increased serum BNP levels, especially in the presence of malignancy.

Management of Pericardial Effusion in Patients With Solid Tumor: An Algorithmic, Multidisciplinary Approach Results in Reduced Mortality After Paradoxical Hemodynamic Instability.

OBJECTIVE: This study compared outcomes in patients with solid tumor treated for pericardial effusion with surgical drainage versus interventional radiology (IR) percutaneous drainage and compared incidence of paradoxical hemodynamic instability (PHI) between cohorts. BACKGROUND: Patients with advanced-stage solid malignancies may develop large pericardial effusions requiring intervention. PHI is a fatal and underreported complication that occurs following pericardial effusion drainage. METHODS: Clinical characteristics and outcomes were compared between patients with solid tumors who underwent s urgical drainage or IR percutaneous drainage for pericardial effusion from 2010 to 2020. RESULTS: Among 447 patients, 243 were treated with surgical drainage, of which 27 (11%) developed PHI, compared with 7 of 204 patients (3%) who were treated with IR percutaneous drainage ( P =0.002); overall incidence of PHI decreased during the study period. Rates of reintervention (30-day: 1% vs 4%; 90-day: 4% vs 6%, P =0.7) and mortality (30-day: 21% vs 17%, P =0.3; 90-day: 39% vs 37%, P =0.7) were not different between patients treated with surgical drainage and IR percutaneous drainage. For both interventions, OS was shorter among patients with PHI than among patients without PHI (surgical drainage, median [95% confidence interval] OS, 0.89 mo [0.33-2.1] vs 6.5 mo [5.0-8.9], P <0.001; IR percutaneous drainage, 3.7 mo [0.23-6.8] vs 5.0 mo [4.0-8.1], P =0.044). CONCLUSIONS: With a coordinated multidisciplinary approach focusing on prompt clinical and echocardiographic evaluation, triage with bias toward IR percutaneous drainage than surgical drainage and postintervention intensive care resulted in lower incidence of PHI and improved outcomes.

NIRS (Near Infrared Spectroscopy) classification of sliced Duroc dry-cured ham under various packaging systems and storage temperature and time.

The potential of Near Infrared Spectroscopy (NIRS) was assessed for storage temperature discrimination (4 °C ± 2 vs. 20 °C ± 2) and for the prediction of the length of time that sliced Duroc dry-cured ham was in storage, considering the following packaging types; vacuum (n = 133) and modified atmosphere (MAP) (n = 133), without opening the package. The models, obtained by means of Partial least squares-discriminant analysis, indicated successful classification of the product according to storage temperature after validation (accuracy values of 100.00% in vacuum and between 92.00 and 100% in MAP). Furthermore, good accuracy was obtained for the assignments into storage times, with values comprised between 92.31% and 100.00% for samples under vacuum and between 91.00% and 97.00% for those under MAP, in both cases after validation. Thus, NIRS technology could help to support the preservation temperature traceability and the stocks of sliced dry-cured hams.