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BACKGROUND: The Paediatric Difficult Intubation Collaborative identified multiple attempts and persistence with direct laryngoscopy as risk factors for complications in children with difficult tracheal intubations and subsequently engaged in initiatives to reduce repeated attempts and persistence with direct laryngoscopy in children. We hypothesised these efforts would lead to fewer attempts, fewer direct laryngoscopy attempts and decrease complications. METHODS: Paediatric patients less than 18 years of age with difficult direct laryngoscopy were enrolled in the Paediatric Difficult Intubation Registry. We define patients with difficult direct laryngoscopy as those in whom (1) an attending or consultant obtained a Cormack Lehane Grade 3 or 4 view on direct laryngoscopy, (2) limited mouth opening makes direct laryngoscopy impossible, (3) direct laryngoscopy failed in the preceding 6 months, and (4) direct laryngoscopy was deferred due to perceived risk of harm or poor chance of success. We used a 5:1 propensity score match to compare an early cohort from the initial Paediatric Difficult Intubation Registry analysis (August 6, 2012-January 31, 2015, 785 patients, 13 centres) and a current cohort from the Registry (March 4, 2017-March 31, 2023, 3925 patients, 43 centres). The primary outcome was first attempt success rate between cohorts. Success was defined as confirmed endotracheal intubation and assessed by the treating clinician. Secondary outcomes were eventual success rate, number of attempts at intubation, number of attempts with direct laryngoscopy, the incidence of persistence with direct laryngoscopy, use of supplemental oxygen, all complications, and severe complications. FINDINGS: First-attempt success rate was higher in the current cohort (42% vs 32%, OR 1.5 95% CI 1.3-1.8, p

Abstract Regulatory T cells (Treg) are critical players of immune tolerance that develop in the thymus via two distinct developmental pathways involving CD25+Foxp3− and CD25−Foxp3lo precursors. However, the mechanisms regulating the recently identified Foxp3lo precursor pathway remain unclear. Here, we find that the membrane-bound lymphotoxin α1β2 (LTα1β2) heterocomplex is upregulated during Treg development upon TCR/CD28 and IL-2 stimulation. We show that Lta expression limits the maturational development of Treg from Foxp3lo precursors by regulating their proliferation, survival, and metabolic profile. Transgenic reporter mice and transcriptomic analyses further reveal that medullary thymic epithelial cells (mTEC) constitute an unexpected source of IL-4. We demonstrate that LTα1β2-lymphotoxin β receptor-mediated interactions with mTEC limit Treg development by down-regulating IL-4 expression in mTEC. Collectively, our findings identify the lymphotoxin axis as the first inhibitory checkpoint of thymic Treg development that fine-tunes the Foxp3lo Treg precursor pathway by limiting IL-4 availability.

Abstract Introduction This prospective multicentre study evaluates the impact of Palliative Care Unit (PCU) intervention (Experimental Group, EG), during autologous hematopoietic stem cell transplantation (AHSCT) on quality of life (QoL), symptom control and healthcare resource use compared to standard practice (Control Group, CG). We used validated scales on Days 0 (stem cell infusion), + 7 (bone marrow aplasia, acute symptoms) and + 21 (aplasia recovery). Results In 40 patients (20 EG/ 20 CG: 45%/25% female, median age 57.5/59), QoL differed significantly at Day + 7 (EG: median 0.50; CG: -63.00; p

Abstract Background Swine dysentery (SD) is a severe mucohaemorrhagic colitis in pigs caused classically by Brachyspira hyodysenteriae. Although several aspects of B. hyodysenteriae infection dynamic are already described, further research in the early stage of this infection is required. In this study, 7-week-old pigs were orally challenged with B. hyodysenteriae to obtain information about faecal shedding, macro and microscopic intestinal lesions and serum acute phase proteins in pigs at the onset of B. hyodysenteriae shedding (early infection group, n = 8), in pigs with mucohaemorrhagic diarrhoea (acute infection group, n = 8) and in non-infected controls (n = 16). Results First B. hyodysenteriae detection by q-PCR and first loose stools with blood and mucus occurred both at 8 days post-inoculation. The lapse between a positive q-PCR and observation of mucohaemorrhagic diarrhoea ranged from 0 to 3 days, except in a single pig in which this period lasted 5 days. Macroscopic lesions were observed in the large intestine from both infected groups although more frequent and severe in acute infection group. Microscopic observation of the apex mucosa revealed that in early infection only higher ulceration values were observed compared to healthy controls. In contrast, the acute infection group exhibited higher ulceration, neutrophils infiltration and increased mucosal thickness compared to the other two groups. Among the serum biomarkers tested, only haptoglobin, C-reactive protein, and creatine kinase showed a significant increase in pigs in the acute infection period compared to controls, whereas haptoglobin was the only factor with a significant increase at the early infection compared to non-infected animals. Conclusions This study provides new insights about SD and remarks the complex and limited options to perform an early detection of infected animals beyond PCR diagnosis.

Abstract Cancer metabolic reprogramming has been recognized as one of the cancer hallmarks that promote cell proliferation, survival, as well as therapeutic resistance. Up-to-date regulation of metabolism in T-cell lymphoma is poorly understood. In particular, for human angioimmunoblastic T-cell lymphoma (AITL) the metabolic profile is not known. Metabolic intervention could help identify new treatment options for this cancer with very poor outcomes and no effective medication. Transcriptomic analysis of AITL tumor cells, identified that these cells use preferentially mitochondrial metabolism. By using our preclinical AITL mouse model, mimicking closely human AITL features, we confirmed that T follicular helper (Tfh) tumor cells exhibit a strong enrichment of mitochondrial metabolic signatures. Consistent with these results, disruption of mitochondrial metabolism using metformin or a mitochondrial complex I inhibitor such as IACS improved the survival of AITL lymphoma-bearing mice. Additionally, we confirmed a selective elimination of the malignant human AITL T cells in patient biopsies upon mitochondrial respiration inhibition. Moreover, we confirmed that diabetic patients suffering from T-cell lymphoma, treated with metformin survived longer as compared to patients receiving alternative treatments. Taking together, our findings suggest that targeting the mitochondrial metabolic pathway could be a clinically efficient approach to inhibit aggressive cancers such as peripheral T-cell lymphoma.

Abstract The concept of synthetic dimensions works particularly well in atomic physics, quantum optics, and photonics, where the internal degrees of freedom (Zeeman sublevels of the ground state, metastable excited states, or motional states for atoms, and angular momentum states or transverse modes for photons) provide the synthetic space. In this Perspective article we report on recent progress on studies of synthetic dimensions, mostly, but not only, based on the research realized around the Barcelona groups (ICFO, UAB), Donostia (DIPC), Poznan (UAM), Kraków (UJ), and Allahabad (HRI). We describe our attempts to design quantum simulators with synthetic dimensions, to mimic curved spaces, artificial gauge fields, lattice gauge theories, twistronics, quantum random walks, and more.

Abstract Antimicrobial resistance is considered one of the most critical threat for both human and animal health. Recently, reports of infection or colonization by carbapenemase-producing Enterobacterales in companion animals had been described. This study report the first molecular characterization of NDM-producing Enterobacterales causing infections in companion animals from Argentina. Nineteen out of 3662 Enterobacterales isolates analyzed between October 2021 and July 2022 were resistant to carbapenemes by VITEK2C and disk diffusion method, and suspected to be carbapenemase-producers. Ten isolates were recovered from canine and nine from feline animals. Isolates were identified as K. pneumoniae (n = 9), E. coli (n = 6) and E. cloacae complex (n = 4), and all of them presented positive synergy among EDTA and carbapenems disks, mCIM/eCIM indicative of metallo-carbapenemase production and were also positive by PCR for bla NDM gene. NDM variants were determined by Sanger sequencing method. All 19 isolates were resistant to β-lactams and aminoglycosides but remained susceptible to colistin (100%), tigecycline (95%), fosfomycin (84%), nitrofurantoin (63%), minocycline (58%), chloramphenicol (42%), doxycycline (21%), enrofloxacin (5%), ciprofloxacin (5%) and trimethoprim/sulfamethoxazole (5%). Almost all isolates (17/19) co-harbored bla CTX-M plus bla CMY, one harbored bla CTX-M alone and the remaining bla CMY. E. coli and E. cloacae complex isolates harbored bla CTX-M-1/15 or bla CTX-M-2 groups, while all K. pneumoniae harbored only bla CTX-M-1/15 genes. All E. coli and E. cloacae complex isolates harbored bla NDM-1, while in K. pneumoniae bla NDM-1 (n = 6), bla NDM-5 (n = 2), and bla NDM-1 plus bla NDM-5 (n = 1) were confirmed. MLST analysis revealed the following sequence types by species, K. pneumoniae: ST15 (n = 5), ST273 (n = 2), ST11, and ST29; E. coli: ST162 (n = 3), ST457, ST224, and ST1196; E. cloacae complex: ST171, ST286, ST544 and ST61. To the best of our knowledge, this is the first description of NDM-producing E. cloacae complex isolates recovered from cats. Even though different species and clones were observed, it is remarkable the finding of some major clones among K. pneumoniae and E. coli, as well as the circulation of NDM as the main carbapenemase. Surveillance in companion pets is needed to detect the spread of carbapenem-resistant Enterobacterales and to alert about the dissemination of these pathogens among pets and humans.

Abstract Background Post weaning diarrhoea (PWD) causes piglet morbidity and mortality at weaning and is a major driver for antimicrobial use worldwide. New regulations in the EU limit the use of in-feed antibiotics (Ab) and therapeutic zinc oxide (ZnO) to prevent PWD. New approaches to control PWD are needed, and understanding the role of the microbiota in this context is key. In this study, shotgun metagenome sequencing was used to describe the taxonomic and functional evolution of the faecal microbiota of the piglet during the first two weeks post weaning within three experimental groups, Ab, ZnO and no medication, on commercial farms using antimicrobials regularly in the post weaning period. Results Diversity was affected by day post weaning (dpw), treatment used and diarrhoea but not by the farm. Microbiota composition evolved towards the dominance of groups of species such as Prevotella spp. at day 14dpw. ZnO inhibited E. coli overgrowth, promoted higher abundance of the family Bacteroidaceae and decreased Megasphaera spp. Animals treated with Ab exhibited inconsistent taxonomic changes across time points, with an overall increase of Limosilactobacillus reuteri and Megasphaera elsdenii. Samples from non-medicated pigs showed virulence-related functions at 7dpw, and specific ETEC-related virulence factors were detected in all samples presenting diarrhoea. Differential microbiota functions of pigs treated with ZnO were related to sulphur and DNA metabolism, as well as mechanisms of antimicrobial and heavy metal resistance, whereas Ab treated animals exhibited functions related to antimicrobial resistance and virulence. Conclusion Ab and particularly ZnO maintained a stable microbiota composition and functionality during the two weeks post weaning, by limiting E. coli overgrowth, and ultimately preventing microbiota dysbiosis. Future approaches to support piglet health should be able to reproduce this stable gut microbiota transition during the post weaning period, in order to maintain optimal gut physiological and productive conditions.

Este artículo recoge mis anotaciones y mis reflexiones etnográficas, como observadora participante, en la audiencia pública del caso n.° 0011-18-cn –matrimonio igualitario– del 29 de marzo del 2019. Orientada por las preguntas ¿por qué el reconocimiento del matrimonio igualitario es un campo de disputa? y ¿cómo el reconocimiento del matrimonio igualitario se convierte en un campo de disputa del orden moral?, se examinan los mecanismos legales –simbólicos y procedimentales– que se produjeron a través del debate y anuencia en torno a una de las acciones de protección que la Corte Constitucional ecuatoriana tuvo que procesar para reconocer este derecho civil. Esta nota presenta algunos aprendizajes teórico-metodológicos y hallazgos empíricos desprendidos del ejercicio etnográfico dentro de un programa de investigación más amplio.

La presente investigación tiene como objetivo analizar el rendimiento académico, a través de la atención de los estilos de aprendizaje, en la sección de Básica Superior. Para esto se consideró la clasificación de estilos de aprendizaje que se deriva de la Teoría del Aprendizaje Experiencial, propuesta por Kolb. Se desarrolló desde un diseño no experimental, aplicando un cuestionario con escala de Likert a los docentes de Básica Superior de la Escuela Alberto Cruz Murillo, para conocer las distintas perspectivas que prevalecen durante el proceso de enseñanza - aprendizaje. Además, se aplicó el cuestionario de Honey Alonso para diagnosticar los estilos de aprendizaje que predominan entre los estudiantes. Los datos obtenidos permitieron comprender que el estilo reflexivo es el que prevalece en el grupo de clase, mientras que la mayor parte de docentes prestan atención a este estilo con poca frecuencia.

City and the territory present quite broad and complex intellectual challenges that belong to the study in the discipline of urban planning. However, it isn’t intended to detract from the works, techniques and methodologies, but to show that the help of a disciplinary dialogue provides the researcher in urban planning and the student to visualize urban phenomena from another perspective and maintain a different vocabulary that allows validating the studies in the territory.This work aims, in the first instance, to reflect, question and induce the reader to a way of visualizing urban planning with a view to expressing what is happening in the territory in a measurable and quantitative way and that gives an articulated discourse to urban expression under the search for new hybrid tools that help direct urban study procedures through the principles of generating urbanometrics in research.The second objective is to present a statistical model that shows the relationship applied between economic units and size of the territory in the Xalapa’s Metropolitan area whose purpose is to demonstrate that urban phenomena can be measured under statistical techniques validated in conjunction with research in urban planning.Keywords: City, Urbanometrics, Regional Economic

Objetivos: La miocardiopatía arritmogénica (MCA) es un trastorno cardíaco complejo asociado con arritmias ventriculares (AV). Comprender la relación entre el desacoplamiento mecánico y los cambios estructurales cardíacos en pacientes con MCA es crucial para una estratificación de riesgos y una gestión mejorada. Métodos: En este estudio, reclutamos a 25 pacientes con MCA (edad media 34 años, 72% hombres) basándonos en los criterios del Task Force 2019 y los criterios de Padua. Los pacientes se clasificaron según la presencia o ausencia de taquicardia ventricular clínicamente relevante (crVT), que requería intervenciones de emergencia. Se evaluó el acoplamiento ventricular derecho-arterial (VAC) mediante ecocardiografía. Se utilizaron low-rank regression splines para modelar la fracción de eyección del ventrículo izquierdo (FEVI) y la fracción de eyección del ventrículo derecho (FEVD) en relación con el VAC. Resultados: Se observaron asociaciones positivas entre el VAC y la FEVI (ρ = 0.472, p = 0.023), la FEVD (ρ = 0.522, p = 0.038) y el volumen de eyección indexado del ventrículo derecho (ρ = 0.79, p < 0.001). Los pacientes con crVT mostraron correlaciones con acortamiento del ventrículo derecho, disminución de la FEVD (39.6 vs. 32.2%, p = 0.025), aumento de la masa ventricular izquierda (38.99 vs. 45.55, p = 0.045) y volumen diastólico final del ventrículo izquierdo (VDVI) (56.99 vs. 68.15 mL/m2, p = 0.045). Se observaron asociaciones positivas para el VAC con el VDVI (p = 0.039) y la masa ventricular izquierda (p = 0.039), mientras que se observaron correlaciones negativas con la FEVD por RMC (p = 0.023) y el acortamiento del ventrículo derecho por ecocardiografía (p = 0.026). Conclusiones: Nuestros hallazgos subrayan la importancia del VAC derecho en la MCA, demostrando correlaciones con la FEVD y FEVI, el volumen de eyección del ventrículo derecho y arritmias clínicamente relevantes. Las percepciones sobre la FEVD, la masa ventricular izquierda y el volumen diastólico final proporcionan contribuciones valiosas para comprender la fisiopatología de la MCA y pueden informar estrategias de evaluación de riesgos.