Role of Tonsillar Chronic Inflammation and Commensal Bacteria in the Pathogenesis of Pediatric OSA

Immune responses at the boundary between the host and the world beyond are complex and mucosal tissue homeostasis relies on them. Obstructive sleep apnea (OSA) is a syndrome suffered by children with hypertrophied tonsils. We have previously demonstrated that these tonsils present a defective regulatory B cell (Breg) compartment. Here, we extend those findings by uncovering the crucial role of resident pro-inflammatory B and T cells in sustaining tonsillar hypertrophy and hyperplasia by producing TNFα and IL17, respectively, in ex vivo cultures. Additionally, we detected prominent levels of expression of CD1d by tonsillar stratified as well as reticular epithelium, which have not previously been reported. Furthermore, we evidenced the hypertrophy of germinal centers (GC) and the general hyperplasia of B lymphocytes within the tissue and the lumen of the crypts. Of note, such B cells resulted mainly (IgG/IgM)+ cells, with some IgA+ cells located marginally in the follicles. Finally, by combining bacterial culture from the tonsillar core and subsequent identification of the respective isolates, we determined the most prevalent species within the cohort of OSA patients. Although the isolated species are considered normal oropharyngeal commensals in children, we confirmed their capacity to breach the epithelial barrier. Our work sheds light on the pathological mechanism underlying OSA, highlighting the relevance taken by the host immune system when defining infection versus colonization, and opening alternatives of treatment.Fil: Sarmiento Varon, Lindybeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: de Rosa, Javier Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Rodriguez, Raquel Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Fernandez, Pablo Mariano. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Billordo, Luis Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Baz, Placida. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Beccaglia, Gladys. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Spada, Nicolás. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Mendoza, F. Tatiana. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; ArgentinaFil: Barberis, María Claudia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; ArgentinaFil: Vay, Carlos. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; ArgentinaFil: Arabolaza, M. Elena. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Paoli, Bibiana Patricia. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Arana, Eloisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentin

Management and outcomes of patients with left atrial appendage thrombus prior to percutaneous closure

Altres ajuts: Fundación Interhospitalaria para la Investigación Cardiovascular (FIC Foundation); Abbott.Objective: Left atrial appendage (LAA) thrombus has heretofore been considered a contraindication to percutaneous LAA closure (LAAC). Data regarding its management are very limited. The aim of this study was to analyse the medical and invasive treatment of patients referred for LAAC in the presence of LAA thrombus. Methods: This multicentre observational registry included 126 consecutive patients referred for LAAC with LAA thrombus on preprocedural imaging. Treatment strategies included intensification of antithrombotic therapy (IAT) or direct LAAC. The primary and secondary endpoints were a composite of bleeding, stroke and death at 18 months, and procedural success, respectively. Results: IAT was the preferred strategy in 57.9% of patients, with total thrombus resolution observed in 60.3% and 75.3% after initial and subsequent IAT, respectively. Bleeding complications and stroke during IAT occurred in 9.6% and 2.9%, respectively, compared with 3.8% bleeding and no embolic events in the direct LAAC group before the procedure. Procedural success was 90.5% (96.2% vs 86.3% in direct LAAC and IAT group, respectively, p=0.072), without cases of in-hospital thromboembolic complications. The primary endpoint occurred in 29.3% and device-related thrombosis was found in 12.8%, without significant difference according to treatment strategy. Bleeding complications at 18 months occurred in 22.5% vs 10.5% in the IAT and direct LAAC group, respectively (p=0.102). Conclusion: In the presence of LAA thrombus, IAT was the initial management strategy in half of our cohort, with initial thrombus resolution in 60% of these, but with a relatively high bleeding rate (∼10%). Direct LAAC was feasible, with high procedural success and absence of periprocedural embolic complications. However, a high rate of device-related thrombosis was detected during follow-up

Overview of the techniques used for the study of non-terrestrial bodies: Proposition of novel non-destructive methodology

Meteorites and impact glasses have been largely analysed using different techniques, but most studies have been focused on their geologicalemineralogical characterization and isotopic ratios, mainly of a destructive nature. However, much more information can be gained by applying novel non-destructive analytical procedures and techniques that have been scarcely used to analyse these materials. This overview presents some new methodologies to study these materials and compares these new approaches with the commonly used ones. Techniques such as X-Ray Fluorescence (XRF) and Laser Induced Breakdown Spectroscopy (LIBS), for elemental characterization, the hyphenated Raman spectroscopy- SEM/EDS and the combination of them, allow extracting simultaneous information from elemental, molecular and structural data of the studied sample; furthermore, the spectroscopic image capabilities of such techniques allow a better understanding of the mineralogical distribution. © 2017 Elsevier B.V. All rights reserved.Ministerio de Economía, Industria y Competitividad (project ESP2014-56138-C3-2-R

Caracterización multianalítica de meteorito marciano NWA2975 mediante CF-LIBS, fluorescencia de rayos X y espectroscopía Raman

La caracterización isotópica y elemental de los meteoritos de Marte ha permitido determinar la cronología de los procesos de formación del planeta y avanzar en la comprensión de su evolución biogeoquímica e hidrológica. Los meteoritos más abundantes son las rocas de origen ígneo, como las shergottitas. Los estudios petrológicos y geoquímicos previos del meteorito Northwest Africa 2975 (NWA 2975), revelaron que se trata de una roca volcánica de grano medio, entre subofítica y granular, compuesta predominantemente por piroxenos (57,3 vol.%) y plagioclasa (38,3 vol. %) completamente enmascarados con fases opacas (2,7 vol.%) y fosfatos (1,7 vol.%) [1]. El instrumento SuperCam a bordo del rover Perseverance (misión MARS 2020 de la NASA) está equipado con técnicas atómicas y moleculares (incluyendo LIBS y Raman) para la detección y análisis a distancia de muestras geológicas en la superficie del Planeta Rojo. La capacidad de estas técnicas se ha demostrado ampliamente en la caracterización de rocas, minerales y suelos en varias misiones espaciales. En el presente trabajo, se analizó un fragmento del meteorito NWA 2975 mediante un sistema de micro-LIBS con el objetivo de revelar su composición química elemental. Debido a la heterogeneidad intrínseca de la muestra, se analizaron diferentes posiciones de su superficie. El análisis cuantitativo de los elementos principales (Si, Al, Fe, Mg, Mn, Ca y O) y de otros elementos menores se llevó a cabo utilizando la metodología Calibration-Free [2]. Los resultados sugieren la presencia de piroxenos como principal componente mineral en las posiciones inspeccionadas, aunque también se pueden encontrar otras fases minerales como la plagioclasa. La información extraída del análisis LIBS se ha comparado con la de fluorescencia de rayos X (XRF) y la espectroscopia Raman. El uso combinado de diferentes técnicas espectroscópicas ha permitido obtener una mejor interpretación de los resultados composicionales.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Dental Health and Mortality in People With End-Stage Kidney Disease Treated With Hemodialysis: A Multinational Cohort Study

Background Dental disease is more extensive in adults with chronic kidney disease, but whether dental health and behaviors are associated with survival in the setting of hemodialysis is unknown. Study Design Prospective multinational cohort. Setting & Participants 4,205 adults treated with long-term hemodialysis, 2010 to 2012 (Oral Diseases in Hemodialysis [ORAL-D] Study). Predictors Dental health as assessed by a standardized dental examination using World Health Organization guidelines and personal oral care, including edentulousness; decayed, missing, and filled teeth index; teeth brushing and flossing; and dental health consultation. Outcomes All-cause and cardiovascular mortality at 12 months after dental assessment. Measurements Multivariable-adjusted Cox proportional hazards regression models fitted with shared frailty to account for clustering of mortality risk within countries. Results During a mean follow-up of 22.1 months, 942 deaths occurred, including 477 cardiovascular deaths. Edentulousness (adjusted HR, 1.29; 95% CI, 1.10-1.51) and decayed, missing, or filled teeth score ≥ 14 (adjusted HR, 1.70; 95% CI, 1.33-2.17) were associated with early all-cause mortality, while dental flossing, using mouthwash, brushing teeth daily, spending at least 2 minutes on oral hygiene daily, changing a toothbrush at least every 3 months, and visiting a dentist within the past 6 months (adjusted HRs of 0.52 [95% CI, 0.32-0.85], 0.79 [95% CI, 0.64-0.97], 0.76 [95% CI, 0.58-0.99], 0.84 [95% CI, 0.71-0.99], 0.79 [95% CI, 0.65-0.95], and 0.79 [95% CI, 0.65-0.96], respectively) were associated with better survival. Results for cardiovascular mortality were similar. Limitations Convenience sample of clinics. Conclusions In adults treated with hemodialysis, poorer dental health was associated with early death, whereas preventive dental health practices were associated with longer survival

Management and outcomes of patients with left atrial appendage thrombus prior to percutaneous closure.

Left atrial appendage (LAA) thrombus has heretofore been considered a contraindication to percutaneous LAA closure (LAAC). Data regarding its management are very limited. The aim of this study was to analyse the medical and invasive treatment of patients referred for LAAC in the presence of LAA thrombus. This multicentre observational registry included 126 consecutive patients referred for LAAC with LAA thrombus on preprocedural imaging. Treatment strategies included intensification of antithrombotic therapy (IAT) or direct LAAC. The primary and secondary endpoints were a composite of bleeding, stroke and death at 18 months, and procedural success, respectively. IAT was the preferred strategy in 57.9% of patients, with total thrombus resolution observed in 60.3% and 75.3% after initial and subsequent IAT, respectively. Bleeding complications and stroke during IAT occurred in 9.6% and 2.9%, respectively, compared with 3.8% bleeding and no embolic events in the direct LAAC group before the procedure. Procedural success was 90.5% (96.2% vs 86.3% in direct LAAC and IAT group, respectively, p=0.072), without cases of in-hospital thromboembolic complications. The primary endpoint occurred in 29.3% and device-related thrombosis was found in 12.8%, without significant difference according to treatment strategy. Bleeding complications at 18 months occurred in 22.5% vs 10.5% in the IAT and direct LAAC group, respectively (p=0.102). In the presence of LAA thrombus, IAT was the initial management strategy in half of our cohort, with initial thrombus resolution in 60% of these, but with a relatively high bleeding rate (~10%). Direct LAAC was feasible, with high procedural success and absence of periprocedural embolic complications. However, a high rate of device-related thrombosis was detected during follow-up

Improved functionalization of oleic acid-coated iron oxide nanoparticles for biomedical applications

Superparamagnetic iron oxide nanoparticles can providemultiple benefits for biomedical applications in aqueous environments such asmagnetic separation or magnetic resonance imaging. To increase the colloidal stability and allow subsequent reactions, the introduction of hydrophilic functional groups onto the particles’ surface is essential. During this process, the original coating is exchanged by preferably covalently bonded ligands such as trialkoxysilanes. The duration of the silane exchange reaction, which commonly takes more than 24 h, is an important drawback for this approach. In this paper, we present a novel method, which introduces ultrasonication as an energy source to dramatically accelerate this process, resulting in high-quality waterdispersible nanoparticles around 10 nmin size. To prove the generic character, different functional groups were introduced on the surface including polyethylene glycol chains, carboxylic acid, amine, and thiol groups. Their colloidal stability in various aqueous buffer solutions as well as human plasma and serum was investigated to allow implementation in biomedical and sensing applications.status: publishe

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified