No Switching Cooperativity between Coordinated Azo Ligands on Complexes Having {MII(phosphane-κ2P)}2+ (M = Pd, Pt) Scaffolds.

A series of square-planar palladium and platinum compounds with cis-blocking phosphanes and terminal azobenzene ligands [M(dppp)(azo)2](OTf)2 (azo = CN(C6H4)-N═N-(C6H4)CN (iso-cyano), CN(C6H4)-N═N-(C6H5) (iso-Ph)) and [{M2(tpbz)}(azo)4](OTf)4 (azo = CN(C6H4)-N═N-(C6H5) (iso-Ph)) have been synthesized and fully characterized. Similarly to the uncoordinated ligands, the new coordination compounds have shown to be photochemically active with respect to their trans-to-cis isomerization process. Their cis-to-trans back spontaneous reaction have been studied as a function of solvent, temperature and pressure and the corresponding activation parameters determined in order to investigate the mechanism of these transformations. The results obtained are indicative of the operation of a rotational mechanism with no cooperativity between the azo ligands attached to the same metal. Density functional theory calculations have been carried out in order to estimate the relative energies of the different photoisomers for the theoretical interpretation of the experimental data.

Donepezil Nanoemulsion Induces a Torpor-like State with Reduced Toxicity in Nonhibernating Xenopus laevis Tadpoles.

Achieving a reversible decrease of metabolism and other physiological processes in the whole organism, as occurs in animals that experience torpor or hibernation, could contribute to increased survival after serious injury. Using a Bayesian network tool with transcriptomic data and chemical structure similarity assessments, we predicted that the Alzheimer's disease drug donepezil (DNP) could be a promising candidate for a small molecule drug that might induce a torpor-like state. This was confirmed in a screening study with Xenopus laevis tadpoles, a nonhibernator whole animal model. To improve the therapeutic performance of the drug and minimize its toxicity, we encapsulated DNP in a nanoemulsion formulated with low-toxicity materials. This formulation is composed of emulsified droplets <200 nm in diameter that contain 1.250 mM DNP, representing ≥95% encapsulation efficiency. The DNP nanoemulsion induced comparable torpor-like effects to those produced by the free drug in tadpoles, as indicated by reduced swimming motion, cardiac beating frequency, and oxygen consumption, but with an improved biodistribution. Use of the nanoemulsion resulted in a more controlled increase of DNP concentration in the whole organism compared to free DNP, and to a higher concentration in the brain, which reduced DNP toxicity and enabled induction of a longer torpor-like state that was fully reversible. These studies also demonstrate the potential use of Xenopus tadpoles as a high-throughput in vivo screen to assess the efficacy, biodistribution, and toxicity of drug-loaded nanocarriers.

Advanced Myocardial MRI Tissue Characterization Combining Contrast Agent-Free T1-Rho Mapping With Fully Automated Analysis.

BACKGROUND: Myocardial T1-rho (T1ρ) mapping is a promising method for identifying and quantifying myocardial injuries without contrast agents, but its clinical use is hindered by the lack of dedicated analysis tools. PURPOSE: To explore the feasibility of clinically integrated artificial intelligence-driven analysis for efficient and automated myocardial T1ρ mapping. STUDY TYPE: Retrospective. POPULATION: Five hundred seventy-three patients divided into a training (N = 500) and a test set (N = 73) including ischemic and nonischemic cases. FIELD STRENGTH/SEQUENCE: Single-shot bSSFP T1ρ mapping sequence at 1.5 T. ASSESSMENT: The automated process included: left ventricular (LV) wall segmentation, right ventricular insertion point detection and creation of a 16-segment model for segmental T1ρ value analysis. Two radiologists (20 and 7 years of MRI experience) provided ground truth annotations. Interobserver variability and segmentation quality were assessed using the Dice coefficient with manual segmentation as reference standard. Global and segmental T1ρ values were compared. Processing times were measured. STATISTICAL TESTS: Intraclass correlation coefficients (ICCs) and Bland-Altman analysis (bias ±2SD); Paired Student's t-tests and one-way ANOVA. A P value <0.05 was considered significant. RESULTS: The automated approach significantly reduced processing time (3 seconds vs. 1 minute 51 seconds ± 22 seconds). In the test set, automated LV wall segmentation closely matched manual results (Dice 81.9% ± 9.0) and closely aligned with interobserver segmentation (Dice 82.2% ± 6.5). Excellent ICCs were achieved on a patient basis (0.94 [95% CI: 0.91 to 0.96]) with bias of -0.93 cm2 ± 6.60. There was no significant difference in global T1ρ values between manual (54.9 msec ± 4.6; 95% CI: 53.8 to 56.0 msec, range: 46.6-70.9 msec) and automated processing (55.4 msec ± 5.1; 95% CI: 54.2 to 56.6 msec; range: 46.4-75.1 msec; P = 0.099). The pipeline demonstrated a high level of agreement with manual-derived T1ρ values at the patient level (ICC = 0.85; bias +0.52 msec ± 5.18). No significant differences in myocardial T1ρ values were found between methods across the 16 segments (P = 0.75). DATA CONCLUSION: Automated myocardial T1ρ mapping shows promise for the rapid and noninvasive assessment of heart disease. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 1.

Sequential Enzymatic Hydrolysis and Ultrasound Pretreatment of Pork Liver for the Generation of Bioactive and Taste-Related Hydrolyzates.

In the study of protein-rich byproducts, enzymatic hydrolysis stands as a prominent technique, generating bioactive peptides. Combining exo- and endopeptidases could enhance both biological and sensory properties. Ultrasound pretreatment is one of the most promising techniques for the optimization of enzymatic hydrolysis. This research aimed to create tasteful and biologically active pork liver hydrolyzates by using sequential hydrolysis with two types of enzymes and two types of ultrasound pretreatments. Sequential hydrolyzates exhibited a higher degree of hydrolysis than single ones. Protana Prime hydrolyzates yielded the largest amount of taste-related amino acids, enhancing sweet, bittersweet, and umami amino acids according to the Taste Activity Value (TAV). These hydrolyzates also displayed significantly higher antioxidant activity. Among sequential hydrolyzates, Flavourzyme and Protana Prime hydrolyzates pretreated with ultrasound showed the highest ferrous ion chelating activity. Overall, employing both Alcalase and Protana Prime on porcine livers pretreated with ultrasound proved to be highly effective in obtaining potentially tasteful and biologically active hydrolyzates.

Structure-Activity Relationship of Natural Dihydrochalcones and Chalcones, and Their Respective Oxyalkylated Derivatives as Anti-Saprolegnia Agents.

Saprolegnia sp. is a pathogenic oomycete responsible for severe economic losses in aquaculture. To date, there is no treatment for its control that is effective and does not pose a threat to the environment and human health. In this research, two dihydrochalcones 1 and 2, and three chalcones 3-5, isolated from the resinous plant Adesmia balsamica, as well as their synthesized oxyalkylated derivatives 6-29 already reported and a new synthesized series of oxyalkylchalcones 30-35, were evaluated for their anti-saprolegnia activity and structure-activity relationship as potential control and treatment agents for strains of Saprolegnia parasitica and S. australis. Among the molecules tested, natural 2',4'-dihydroxychalcone (3) and new oxyalkylchalcone 34 were the most potent antisaprolegnia agents against both strains, even with better results than the commercial control bronopol. On the other hand, the structure-activity relationship study indicates that the contributions of steric and electrostatic fields are important to enhance the activity of the compounds, thus the presence of bulky substituents favors the activity.

Variation in the Floral Morphology of Prosthechea karwinskii (Orchidaceae), a Mexican Endemic Orchid at Risk.

Prosthechea karwinskii is an orchid endemic to Mexico, threatened by the destruction of its habitat and the extraction of specimens to meet its demand for ornamental and religious use. Most of its populations, including the most locally abundant ones, are found in Oaxaca state. Variations in some floral traits have been observed in these populations. We implemented a morphometric analysis to assess their floral variation and identify the most significant characters in the morphological patterns of this orchid. Floral samples were collected from 17 populations of P. karwinskii in Oaxaca, as well as from specimens used as ornaments during Easter in an Oaxacan community (Zaachila), whose origin is unknown. Sampling of natural populations covered the environmental, geographic, and morphological variation of the species. We performed an analysis of variance (ANOVA), principal component analysis (PCA), canonical variate analysis (CVA), and cluster analysis, including 185 individuals and 45 variables (12 of them were discarded in the multivariate analyses due to high correlation). Characters of the column, lateral sepal, and labellum were most informative for the observed morphological patterns. Albarradas showed the greatest morphological differentiation, mainly due to the column. In general, individuals from the same locality tended to overlap more, especially the populations of Jaltianguis and Yahuiche, which were different from the geographically close population of Etla. Teposcolula presented the highest values in perianth characters, unlike Sola_Rancho Viejo. The specimens recovered from religious ornaments were morphologically more similar to those from Yanhuitlan and Etla. This morphometric analysis identified characters as potential taxonomic markers for P. karwinskii and related species, showing its potential to associate specimens of unknown origin with their probable geographical region. Our work encourages working on collaborative conservation strategies to ensure the long-term permanence of both the species and its traditional uses.

The temporal mismatch across listening sides affects cortical auditory evoked responses in normal hearing listeners and cochlear implant users with contralateral acoustic hearing.

Combining a cochlear implant with contralateral acoustic hearing typically enhances speech understanding, although this improvement varies among CI users and can lead to an interference effect. This variability may be associated with the effectiveness of the integration between electric and acoustic stimulation, which might be affected by the temporal mismatch between the two listening sides. Finding methods to compensate for the temporal mismatch might contribute to the optimal adjustment of bimodal devices and to improve hearing in CI users with contralateral acoustic hearing. The current study investigates cortical auditory evoked potentials (CAEPs) in normal hearing listeners (NH) and CI users with contralateral acoustic hearing. In NH, the amplitude of the N1 peak and the maximum phase locking value (PLV) were analyzed under monaural, binaural, and binaural temporally mismatched conditions. In CI users, CAEPs were measured when listening with CI only (CIS_only), acoustically only (AS_only) and with both sides together (CIS+AS). When listening with CIS+AS, various interaural delays were introduced between the electric and acoustic stimuli. In NH listeners, interaural temporal mismatch resulted in decreased N1 amplitude and PLV. Moreover, PLV is suggested as a more sensitive measure to investigate the integration of information between the two listening sides. CI users showed varied N1 latencies between the AS_only and CIS_only listening conditions, with increased N1 amplitude when the temporal mismatch was compensated. A tendency towards increased PLV was also observed, however, to a lesser extent than in NH listeners, suggesting a limited integration between electric and acoustic stimulation. This work highlights the potential of CAEPs measurement to investigate cortical processing of the information between two listening sides in NH and bimodal CI users.

The beating heart: artificial intelligence for cardiovascular application in the clinic.

Artificial intelligence (AI) integration in cardiac magnetic resonance imaging presents new and exciting avenues for advancing patient care, automating post-processing tasks, and enhancing diagnostic precision and outcomes. The use of AI significantly streamlines the examination workflow through the reduction of acquisition and postprocessing durations, coupled with the automation of scan planning and acquisition parameters selection. This has led to a notable improvement in examination workflow efficiency, a reduction in operator variability, and an enhancement in overall image quality. Importantly, AI unlocks new possibilities to achieve spatial resolutions that were previously unattainable in patients. Furthermore, the potential for low-dose and contrast-agent-free imaging represents a stride toward safer and more patient-friendly diagnostic procedures. Beyond these benefits, AI facilitates precise risk stratification and prognosis evaluation by adeptly analysing extensive datasets. This comprehensive review article explores recent applications of AI in the realm of cardiac magnetic resonance imaging, offering insights into its transformative potential in the field.

Plant Cyanogenic-Derived Metabolites and Herbivore Counter-Defences.

The release of cyanide from cyanogenic precursors is the central core of the plant defences based on the cyanogenesis process. Although cyanide is formed as a coproduct of some metabolic routes, its production is mostly due to the degradation of cyanohydrins originating from cyanogenic glycosides in cyanogenic plants and the 4-OH-ICN route in Brassicaceae. Cyanohydrins are then hydrolysed in a reversible reaction generating cyanide, being both, cyanohydrins and cyanide, toxic compounds with potential defensive properties against pests and pathogens. Based on the production of cyanogenic-derived molecules in response to the damage caused by herbivore infestation, in this review, we compile the actual knowledge of plant cyanogenic events in the plant-pest context. Besides the defensive potential, the mode of action, and the targets of the cyanogenic compounds to combat phytophagous insects and acari, special attention has been paid to arthropod responses and the strategies to overcome the impact of cyanogenesis. Physiological and behavioural adaptations, as well as cyanide detoxification by ß-cyanoalanine synthases, rhodaneses, and cyanases are common ways of phytophagous arthropods defences against the cyanide produced by plants. Much experimental work is needed to further understand the complexities and specificities of the defence-counter-defence system to be applied in breeding programs.

Size Control of Chiral Nanospheres Obtained via Nanoprecipitation of Helical Poly(phenylacetylene)s in the Absence of Surfactants.

Nanostructuration of dynamic helical polymers such as poly(phenylacetylene)s (PPAs) depends on the secondary structure adopted by the polymer and the functional group used to connect the chiral pendant to the PPA backbone. Thus, while PPAs with dynamic and flexible scaffolds (para- and meta-substituted, ω1<165°) generate by nanoprecipitation low polydisperse nanospheres with controllable size at different acetone/water mixtures, those with a quasi-static behavior and the presence of an extended, almost planar structure (ortho-substituted, ω1>165°), aggregate into a mixture of spherical and oval nanostructures whose size is not controlled. Photostability studies show that poly(phenylacetylene) particles are more stable to light irradiation than when dissolved macromolecularly. Moreover, the photostability of the particle depends on the secondary structure of the PPA and its screw sense excess. This fact, in combination with the encapsulation ability of these polymer particles, allows the creation of light stimuli-responsive nanocarriers, whose cargo can be delivered by light irradiation.

Cost-effectiveness analysis of the diagnosis of temporal arteritis.

Temporal arteritis (TA) is the most common form of systemic vasculitis. Its diagnosis is based on criteria proposed by the American College of Rheumatology (1990), and its treatment is high-dose corticosteroids. Our objective is to assess the cost of diagnosing TA, and secondarily, cost-effective analysis of different diagnostic strategies (clinical, biopsy, doppler ultrasound) and therapeutic strategies (corticosteroid suspension). MATERIAL AND METHOD: Observational, retrospective study has been carried out on patients with AT (2012-2021). Demographic data, comorbidities, signs and symptoms suggestive of AT were collected. AT was diagnosed with a score ≥ 3 according to American College of Rheumatoloy criteria (ACR-SCORE). The costs of diagnosis and treatment modification were analysed. RESULTS: Seventy-five patients have been included, median age 77 (46-87) years. Headache, temporal pain and jaw claudication were significant for the diagnosis of TA. Patients with a halo on Doppler ultrasound and a positive biopsy have significantly elevated ESR and CRP compared to patients who do not. The cost of the AT diagnosis was 414.7 euros/patient. If we use ACR-SCORE ≥ 3-echodoppler it is 167.2 є/patient (savings 59.6%) and ACR-SCORE ≥ 3-biopsy 339.75 є/patient (savings 18%). If the corticosteroid was removed and a biopsy was performed, 21.6 є/patient (94.7% savings), if the corticosteroid was removed and Doppler ultrasound was performed, 10.6 є/patient (97.4% savings). CONCLUSIONS: Headache, temporary pain and jaw claudication are predictors of AT. Elevated ESR and CRP are predictors of positive biopsy and presence of halo on ultrasound. The uses of ACR-SCORE ≥ 3 with Doppler ultrasound or biopsy, and with corticosteroid suspension, are cost-effective.

Fully automated contrast selection of joint bright- and black-blood late gadolinium enhancement imaging for robust myocardial scar assessment.

PURPOSE: Joint bright- and black-blood MRI techniques provide improved scar localization and contrast. Black-blood contrast is obtained after the visual selection of an optimal inversion time (TI) which often results in uncertainties, inter- and intra-observer variability and increased workload. In this work, we propose an artificial intelligence-based algorithm to enable fully automated TI selection and simplify myocardial scar imaging. METHODS: The proposed algorithm first localizes the left ventricle using a U-Net architecture. The localized left cavity centroid is extracted and a squared region of interest ("focus box") is created around the resulting pixel. The focus box is then propagated on each image and the sum of the pixel intensity inside is computed. The smallest sum corresponds to the image with the lowest intensity signal within the blood pool and healthy myocardium, which will provide an ideal scar-to-blood contrast. The image's corresponding TI is considered optimal. The U-Net was trained to segment the epicardium in 177 patients with binary cross-entropy loss. The algorithm was validated retrospectively in 152 patients, and the agreement between the algorithm and two magnetic resonance (MR) operators' prediction of TI values was calculated using the Fleiss' kappa coefficient. Thirty focus box sizes, ranging from 2.3mm2 to 20.3cm2, were tested. Processing times were measured. RESULTS: The U-Net's Dice score was 93.0 ± 0.1%. The proposed algorithm extracted TI values in 2.7 ± 0.1 s per patient (vs. 16.0 ± 8.5 s for the operator). An agreement between the algorithm's prediction and the MR operators' prediction was found in 137/152 patients (κ= 0.89), for an optimal focus box of size 2.3cm2. CONCLUSION: The proposed fully-automated algorithm has potential of reducing uncertainties, variability, and workload inherent to manual approaches with promise for future clinical implementation for joint bright- and black-blood MRI.

Epidemiological Overview of Overweight and Obesity Related to Eating Habits, Physical Activity and the Concurrent Presence of Depression and Anxiety in Adolescents from High Schools in Mexico City: A Cross-Sectional Study.

Overweight and obesity in adolescents has become a serious public health problem worldwide and Mexico City is no exception. Therefore, the objective of this study was to investigate the epidemiological panorama of overweight and obesity related to eating habits, physical activity and the concurrent presence of depression and anxiety in adolescents from high schools in Mexico City. Anthropometric measurements were taken from 2710 adolescents from 33 participating high schools. Likewise, a previously validated eating habit and physical activity questionnaire was administered, which consisted of four different sections, where each of the sections focused on key aspects of the participants' lifestyle: (1) eating habits, (2) intake of non-recommended foods, (3) food and company environment, and (4) physical activity. Moreover, the Hospital Anxiety and Depression Scale (HADS) for anxiety and depression was applied. In this study, a high prevalence of overweight and obesity (26.5% overweight and 20.0% obese) was found in adolescents from high schools in Mexico City. Only 13.14% of participants had adequate eating habits and 18.19% physical activity habits. An association was found between having inadequate eating habits and obesity in adolescent women (OR = 1.95; CI 1.009-3.76). Additionally, associations were observed between depression symptoms and obesity (OR = 5.68, CI 1.36-32.81; p = 0.01), while anxiety was associated with underweight and obesity adjusted by other dietary habits and psychological factors. Therefore, it is important to identify adolescents with overweight or obesity and establish prevention strategies for weight control in this age group, promoting healthy eating, physical activity and education in mental health.

Physiotherapy Interventions in Lung Cancer Patients: A Systematic Review.

BACKGROUND: Lung cancer is a very common disease and leads to a series of sequelae such as reduced lung capacity or reduced functional capacity in patients, which are associated not only with the disease itself, but also with medical treatment. Thus, physiotherapeutic interventions are needed to improve quality of life and reduce these symptoms. OBJECTIVES: To find out the effects of physiotherapy on functional capacity, lung capacity, dyspnea, pain, and quality of life in lung cancer patients. METHODS: A systematic review was carried out in five databases. Randomized clinical trials published between 2019-2023 were selected, in which the physiotherapeutic treatment was physical exercise and/or respiratory physiotherapy. RESULTS: Nine articles were included, in which the total sample consisted of 635 lung cancer patients. When combined, respiratory physiotherapy and physical exercise improved functional capacity and lung capacity (p < 0.05). Dyspnea also improved, but less significance was shown in the included studies. CONCLUSIONS: Multimodal physiotherapy interventions may offer benefits for some lung cancer patients, but the extent and nature of these benefits may vary depending on the intervention applied. Therefore, it would be of great interest to carry out further scientific research to support this conclusion.

The RIN4-like/NOI proteins NOI10 and NOI11 modulate the response to biotic stresses mediated by RIN4 in Arabidopsis.

KEY MESSAGE: NOI10 and NOI11 are two RIN4-like/NOI proteins that participate in the immune response of the Arabidopsis plant and affect the RIN4-regulated mechanisms involving the R-proteins RPM1 and RPS2. The immune response in plants depends on the regulation of signaling pathways triggered by pathogens and herbivores. RIN4, a protein of the RIN4-like/NOI family, is considered to be a central immune signal in the interactions of plants and pathogens. In Arabidopsis thaliana, four of the 15 members of the RIN4-like/NOI family (NOI3, NOI5, NOI10, and NOI11) were induced in response to the plant herbivore Tetranychus urticae. While overexpressing NOI10 and NOI11 plants did not affect mite performance, opposite callose accumulation patterns were observed when compared to RIN4 overexpressing plants. In vitro and in vivo analyses demonstrated the interaction of NOI10 and NOI11 with the RIN4 interactors RPM1, RPS2, and RIPK, suggesting a role in the context of the RIN4-regulated immune response. Transient expression experiments in Nicotiana benthamiana evidenced that NOI10 and NOI11 differed from RIN4 in their functionality. Furthermore, overexpressing NOI10 and NOI11 plants had significant differences in susceptibility with WT and overexpressing RIN4 plants when challenged with Pseudomonas syringae bacteria expressing the AvrRpt2 or the AvrRpm1 effectors. These results demonstrate the participation of NOI10 and NOI11 in the RIN4-mediated pathway. Whereas RIN4 is considered a guardee protein, NOI10 and NOI11 could act as decoys to modulate the concerted activity of effectors and R-proteins.

Laparoscopic versus open approach for interval cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) in advanced epithelial ovarian cancer: a matched comparative study.

BACKGROUND: The use of the laparoscopic approach for the treatment of carcinomatosis from epithelial ovarian cancer (EOC) is controversial. The aim of this study was to compare the short-term outcomes of both laparoscopic and open approach for interval CRS+HIPEC in a matched cohort of patients with advanced EOC. METHODS: A retrospective analysis of a prospectively maintained database including 254 patients treated with interval CRS-HIPEC between January 2016 and December 2021 was performed. Patients with primary disease and limited carcinomatosis (PCI ≤ 10) were selected. A comparative analysis of patients treated by either open (O-CRS-HIPEC) or the laparoscopic (L-CRS-HIPEC) approach was conducted. Overall survival (OS), disease-free survival (DFS), and perioperative outcomes were analysed. RESULTS: Fifty-three patients were finally selected and enrolled into two comparable groups in this study. Of these, 14 patients were treated by interval L-CRS-HIPEC and 39 by interval O-CRS-HIPEC. The L-CRS-HIPEC group had a shorter hospital stay (5.6 ± 1.9 vs. 9.7 ± 9.8 days; p < 0.001) and a shorter time to return to systemic chemotherapy (4.3 ± 1.9 vs. 10.3 ± 16.8 weeks; p = 0.003). There were no significant differences in postoperative complications between both groups. The 2-year OS and DFS was 100% and 62% in the L-CRS-HIPEC group versus 92% and 60% in the O-CRS-HIPEC group, respectively (p = 0.96; p = 0.786). CONCLUSION: This study suggests that the use of interval L-CRS-HIPEC for primary advanced EOC is associated with shorter hospital stay and return to systemic treatment while obtaining similar oncological results compared to the open approach. Further prospective research is needed to recommend this new approach for these strictly selected patients.

Tailored electrocardiographic-based criteria for different pacing locations within the left bundle branch.

BACKGROUND: Electrocardiographic (ECG)-based criteria are used to confirm left bundle branch (LBB) pacing (LBBP), but current cutoff values have never been validated for different pacing locations. OBJECTIVE: The purpose of this study was to describe diagnostic performance of V6-R wave peak time (RWPT), V6-V1 interpeak interval, and aVL-RWPT for different pacing sites within the LBB and to determine 100% specific values for each criterion at each pacing location. METHODS: Consecutive patients with confirmed LBBP were selected. Population was divided into subgroups based on the site of pacing: left bundle trunk pacing (LBTP), left septal fascicular pacing (LSFP), left posterior fascicular pacing (LPFP), and left anterior fascicular pacing (LAFP). RESULTS: A total of 147 patients with unequivocal LBB capture were analyzed. Left fascicular pacing was more frequently achieved (82.8%) than LBTP (17.2%). Diagnostic performance of V6-RWPT, V6-V1 interpeak interval, and aVL-RWPT for discrimination of LBBP was good in all subgroups. V6-RWPT cutoff values with 100% specificity (SP) for LBBP discrimination were 75 ms in LBTP, 68 ms in LPFP, 81 ms in LAFP, and 79.5 ms in LSFP. V6-V1 interpeak interval cutoff values with 100% SP for LBBP discrimination were 35.5 ms in LBTP, 53.5 ms in LPFP, 41 ms in LAFP, and 46 ms in LSFP. In LAFP, aVL-RWPT cutoff value with 100% SP for LBBP discrimination was 68 ms, but was 74 ms in LBTP, 74.5 ms in LSFP, and 73.5 ms in LPFP. CONCLUSIONS: Tailored ECG-based criteria might be useful to confirm LBBP at different pacing locations within the LBB.

Effectiveness of Mepolizumab in Patients with Severe Eosinophilic Asthma with/without Nasal Polyposis: A Real-Life Study.

INTRODUCTION: Asthma is one of the most common chronic diseases and affects around 334 million people worldwide. The estimated prevalence of severe asthma is 3-10% of the asthmatic population. Mepolizumab has demonstrated efficacy in reducing exacerbations, oral corticosteroid use, and improving quality of life, asthma control, and lung function in patients with severe eosinophilic asthma (SEA). Our study aimed to check the response to mepolizumab in a series of severe asthma patients regarding exacerbations, oral corticosteroid use, asthma control, quality of life, and lung function and to compare the response between patients with and without nasal polyps. METHOD: This is a retrospective, multicenter study of RE-ASGRAMUR (Register of Severe Asthma of the Region of Murcia) performed in eight hospitals of the Region of Murcia (Spain) under routine clinical practice conditions. We included patients diagnosed with SEA who completed at least 1 year of treatment with mepolizumab. We analyzed clinical characteristics, drug tolerance, and effectiveness: exacerbations, ACT, miniAQLQ, forced expiratory volume in 1 s (FEV1), and use of oral corticosteroids. We also compared the results between patients with and without nasal polyps. RESULTS: The median of exacerbations before treatment was 3 and decreased to 0 after treatment (mean decrease of 77.4%). The median diary oral prednisone intake was 15 mg before treatment and 5 mg after treatment (mean 56% reduction). We have obtained a significant improvement in other variables: ED visits and hospitalizations, asthma control (ACT), quality of life (miniAQLQ), and lung function (FEV1). Thirty-four out of 70 patients (48.57%) fulfilled the criteria of super-responder, and 17 out of 70 (24.29%) had a complete response. More patients in the group with nasal polyps fulfilled the criteria of super-responder and complete response to mepolizumab. CONCLUSIONS: Mepolizumab is a safe and effective treatment for SEA patients, improving exacerbations, oral corticosteroid intake, asthma control, quality of life, and lung function. In patients with associated nasal polyposis, there is a statistically significant higher proportion of super-responders and complete responders.

Ensembl 2024.

Ensembl (https://www.ensembl.org) is a freely available genomic resource that has produced high-quality annotations, tools, and services for vertebrates and model organisms for more than two decades. In recent years, there has been a dramatic shift in the genomic landscape, with a large increase in the number and phylogenetic breadth of high-quality reference genomes, alongside major advances in the pan-genome representations of higher species. In order to support these efforts and accelerate downstream research, Ensembl continues to focus on scaling for the rapid annotation of new genome assemblies, developing new methods for comparative analysis, and expanding the depth and quality of our genome annotations. This year we have continued our expansion to support global biodiversity research, doubling the number of annotated genomes we support on our Rapid Release site to over 1700, driven by our close collaboration with biodiversity projects such as Darwin Tree of Life. We have also strengthened support for key agricultural species, including the first regulatory builds for farmed animals, and have updated key tools and resources that support the global scientific community, notably the Ensembl Variant Effect Predictor. Ensembl data, software, and tools are freely available.