Neutralizing IFN-γ autoantibodies are rare and pathogenic in HLA-DRB1*15:02 or 16:02 individuals.

BACKGROUNDWeakly virulent environmental mycobacteria (EM) can cause severe disease in HLA-DRB1*15:02 or 16:02 adults harboring neutralizing anti-IFN-γ autoantibodies (nAIGAs). The overall prevalence of nAIGAs in the general population is unknown, as are the penetrance of nAIGAs in HLA-DRB1*15:02 or 16:02 individuals and the proportion of patients with unexplained, adult-onset EM infections carrying nAIGAs.METHODSThis study analyzed the detection and neutralization of anti-IFN-γ autoantibodies (auto-Abs) from 8,430 healthy individuals of the general population, 257 HLA-DRB1*15:02 or 16:02 carriers, 1,063 patients with autoimmune disease, and 497 patients with unexplained severe disease due to EM.RESULTSWe found that anti-IFN-γ auto-Abs detected in 4,148 of 8,430 healthy individuals (49.2%) from the general population of an unknown HLA-DRB1 genotype were not neutralizing. Moreover, we did not find nAIGAs in 257 individuals carrying HLA-DRB1* 15:02 or 16:02. Additionally, nAIGAs were absent in 1,063 patients with an autoimmune disease. Finally, 7 of 497 patients (1.4%) with unexplained severe disease due to EM harbored nAIGAs.CONCLUSIONThese findings suggest that nAIGAs are isolated and that their penetrance in HLA-DRB1*15:02 or 16:02 individuals is low, implying that they may be triggered by rare germline or somatic variants. In contrast, the risk of mycobacterial disease in patients with nAIGAs is high, confirming that these nAIGAs are the cause of EM disease.FUNDINGThe Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH) (R01AI095983 and U19AIN1625568), the National Center for Advancing Translational Sciences (NCATS), the NIH Clinical and Translational Science Award (CTSA) program (UL1 TR001866), the French National Research Agency (ANR) under the "Investments for the Future" program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), ANR-GENMSMD (ANR-16-CE17-0005-01), ANR-MAFMACRO (ANR-22-CE92-0008), ANRSECTZ170784, the French Foundation for Medical Research (FRM) (EQU201903007798), the ANRS-COV05, ANR GENVIR (ANR-20-CE93-003), and ANR AI2D (ANR-22-CE15-0046) projects, the ANR-RHU program (ANR-21-RHUS-08-COVIFERON), the European Union's Horizon 2020 research and innovation program under grant agreement no. 824110 (EASI-genomics), the Square Foundation, Grandir - Fonds de solidarité pour l'enfance, the Fondation du Souffle, the SCOR Corporate Foundation for Science, the Battersea & Bowery Advisory Group, William E. Ford, General Atlantic's Chairman and Chief Executive Officer, Gabriel Caillaux, General Atlantic's Co-President, Managing Director, and Head of business in EMEA, and the General Atlantic Foundation, Institut National de la Santé et de la Recherche Médicale (INSERM) and of Paris Cité University. JR was supported by the INSERM PhD program for doctors of pharmacy (poste d'accueil INSERM). JR and TLV were supported by the Bettencourt-Schueller Foundation and the MD-PhD program of the Imagine Institute. MO was supported by the David Rockefeller Graduate Program, the Funai Foundation for Information Technology (FFIT), the Honjo International Scholarship Foundation (HISF), and the New York Hideyo Noguchi Memorial Society (HNMS).

Probing the Phase Transition to a Coherent 2D Kondo Lattice.

Kondo lattices are systems with unusual electronic properties that stem from strong electron correlation, typically studied in intermetallic 3D compounds containing lanthanides or actinides. Lowering the dimensionality of the system enhances the role of electron correlations providing a new tuning knob for the search of novel properties in strongly correlated quantum matter. The realization of a 2D Kondo lattice by stacking a single-layer Mott insulator on a metallic surface is reported. The temperature of the system is steadily lowered and by using high-resolution scanning tunneling spectroscopy, the phase transition leading to the Kondo lattice is followed. Above 27 K the interaction between the Mott insulator and the metal is negligible and both keep their original electronic properties intact. Below 27 K the Kondo screening of the localized electrons in the Mott insulator begins and below 11 K the formation of a coherent quantum electronic state extended to the entire sample, i.e., the Kondo lattice, takes place. By means of density functional theory, the electronic properties of the system and its evolution with temperature are explained. The findings contribute to the exploration of unconventional states in 2D correlated materials.

Resonant Photoionization of CO2 up to the Fourth Ionization Threshold.

We present a comprehensive theoretical study of valence-shell photoionization of the CO2 molecule by using the XCHEM methodology. This method makes use of a fully correlated molecular electronic continuum at a level comparable to that provided by state-of-the-art quantum chemistry packages in bound-state calculations. The calculated total and angularly resolved photoionization cross sections are presented and discussed, with particular emphasis on the series of autoionizing resonances that appear between the first and the fourth ionization thresholds. Ten series of Rydberg autoionizing states are identified, including some not previously reported in the literature, and their energy positions and widths are provided. This is relevant in the context of ongoing experimental and theoretical efforts aimed at observing in real-time (attosecond time scale) the autoionization dynamics in molecules.

Modelling and testing forest ecosystems condition account.

We developed an application model based on the System of Environmental Economic Accounting-Ecosystem Accounting (SEEA-EA) framework, endorsed by the United Nations Statistical Commission in 2021. This model enables mapping condition accounts for forest ecosystems using automated computation. We applied the model nationally in Spain between 2000 and 2015 to test its effectiveness. Our model follows five methodological steps to generate forest condition accounts: (i) definition and spatial delimitation of forest ecosystem types; (ii) selection of variables using the ecosystem condition typology encompassing physical, chemical, compositional, structural, functional, and landscape characteristics; (iii) establishment of reference levels, including lower (collapse) and upper (high ecosystem integrity) thresholds; (iv) aggregation of variables into condition index; and (v) calculation of a single condition index by rescaling the aggregated indicators between 0 and 1. The results obtained from the model provide valuable insights into the status and trends of individual condition indicators, as well as aggregated condition index values for forest ecosystems, in a spatially explicit manner. Overall, the condition of the forest ecosystems in Spain showed a slight increase, from 0.56 in 2000 to 0.58 in 2015. However, distinct trends were observed for each ecosystem type. For example, mixed Alpine and Macaronesia forests exhibited a significant improvement, while the continental Mediterranean coniferous forests did not show any change. This innovative approach to monitoring forest condition accounts has important potential applications in policy and decision-making processes. It can contribute to effective evidence-based nature conservation, ecosystem service management, and identifying restoration areas.

Bienestar subjetivo y satisfacciones de dominios en estudiantes universitarios colombianos / Subjective well-being and domain satisfactions in Colombian university students

Resumen El concepto de bienestar subjetivo se refiere a la forma global, positiva o negativa, en la que las personas evalúan sus vidas y experiencias. La búsqueda de factores que expliquen el bienestar subjetivo, actualmente uno de los temas de mayor interés en la psicología, condujo al concepto de satisfacciones de dominios, que se entienden como los juicios que las personas hacen al evaluar los mayores dominios de vida. Este estudio correlacional tuvo por objetivo establecer la relación de la satisfacción en los dominios económico, de pareja, familia, amigos, salud, vida universitaria y rendimiento académico, con los componentes cognitivo y emocional del bienestar subjetivo (satisfacción vital y felicidad, respectivamente), identificando cuáles de esos dominios lo predicen. La muestra, no probabilística, estuvo conformada por 344 estudiantes de una universidad pública colombiana (50.9 % mujeres y 49.1 % hombres) con edades entre 18 y 29 años (. = 20.89; DT = 2.52). Los resultados mostraron una fuerte relación de todos los dominios con el bienestar subjetivo. La satisfacción en los dominios económico, de pareja, familia, amigos y vida universitaria explicó la varianza de la satisfacción vital y la felicidad en forma diferenciada. Se concluye que: (a) el bienestar se afecta con la satisfacción de necesidades asociadas a los dominios cercanos e importantes para el individuo; (b) las satisfacciones de dominios impactan más el componente cognitivo del bienestar que el emocional; (c) el dominio económico satisface más necesidades cognitivas, la amistad suple necesidades emocionales, y la pareja, la familia y la vida universitaria satisfacen ambas.

Abstract The concept of subjective well-being refers to the overall positive or negative way in which people evaluate their lives and experiences. It is generally accepted that subjective well-being is made up of a cognitive component usually called satisfaction with life or life satisfaction and an emotional component usually referred to as happiness. The search for factors that explain subjective well-being is currently one of the most interesting topics in psychology and led to the concept of domain satisfactions, which are understood as the judgments that people make when evaluating the major domains of life. It refers to the perceived degree of satisfaction that we obtain from the way in which each of these main domains or areas of our lives are developed. This correlational study with predictive intent aimed at establishing the relationship of satisfaction in the economic, couple, family, friends, health, university life, and academic performance domains, with the cognitive and emotional components of subjective well-being (life satisfaction and happiness, respectively), identifying which of these domains predict well-being. The non-probabilistic sample, for convenience, was made up of 344 women and men (50.9 % and 49.1 % respectively) between 18 and 29 years of age (M = 20.89); SD = 2.52), students from an important Colombian public university based in the city of Palmira. The instruments, which include the Diener's life satisfaction and Lyubomirsky and Lepper's happiness scales, and simple items for each domain satisfaction studied (economic, couple, family, friends, health, university life, and academic performance) were answered in a format printed by 64 % of the participants and in virtual format by 36 %, according to their own choice. The results showed that all domain satisfactions were significantly related to both the cognitive and the emotional components of subjective well-being. The results also showed that except for satisfaction with health and academic performance, all other domain satisfactions predicted at least one of the components of subjective well-being. In general, domain satisfactions explained the variance of satisfaction and happiness much better than sociodemographic variables. Thus, it was confirmed that the psychological significance of events that occur in the main areas of people´s lives have much more relevance to well-being than situational factors such as sociodemographic ones. In a different sense, and order of impact, satisfaction with the economic domain, satisfaction with university life, and satisfaction with the couple emerged as the domains that had the greatest influence on life satisfaction, and satisfaction with friends and satisfaction with university life emerged as the strongest predictors of happiness. The results suggest that well-being is especially affected by the satisfaction of needs associated with the closest domains and more important to the individual. These would include the economic domain and relationships that involve affections, but also other domains that, for specific reasons, occupy a relevant place in the individual's internal hierarchy of importance, which may vary among cultures and even among people of the same culture. The above conclusion could explain, among other findings, the significant impact of satisfaction with university life on subjective well-being. The results also suggest that, in general, domain satisfactions have a greater impact on the cognitive component of well-being than on the emotional component, and that, in particular, domains such as economics fundamentally satisfy cognitive needs, friendship fundamentally satisfy emotional needs, and other domains such as couple, family and university life, satisfy both cognitive and emotional needs. This would demonstrate the importance of applying differentiated instruments to study the cognitive and emotional components of well-being.

Attosecond delays between dissociative and non-dissociative ionization of polyatomic molecules.

The interplay between electronic and nuclear motions in molecules is a central concept in molecular science. To what extent it influences attosecond photoionization delays is an important, still unresolved question. Here, we apply attosecond electron-ion coincidence spectroscopy and advanced calculations that include both electronic and nuclear motions to study the photoionization dynamics of CH4 and CD4 molecules. These molecules are known to feature some of the fastest nuclear dynamics following photoionization. Remarkably, we find no measurable delay between the photoionization of CH4 and CD4, neither experimentally nor theoretically. However, we measure and calculate delays of up to 20 as between the dissociative and non-dissociative photoionization of the highest-occupied molecular orbitals of both molecules. Experiment and theory are in quantitative agreement. These results show that, in the absence of resonances, even the fastest nuclear motion does not substantially influence photoionization delays, but identify a previously unknown signature of nuclear motion in dissociative-ionization channels. These findings have important consequences for the design and interpretation of attosecond chronoscopy in molecules, clusters, and liquids.

Imaging and controlling coherent phonon wave packets in single graphene nanoribbons.

The motion of atoms is at the heart of any chemical or structural transformation in molecules and materials. Upon activation of this motion by an external source, several (usually many) vibrational modes can be coherently coupled, thus facilitating the chemical or structural phase transformation. These coherent dynamics occur on the ultrafast timescale, as revealed, e.g., by nonlocal ultrafast vibrational spectroscopic measurements in bulk molecular ensembles and solids. Tracking and controlling vibrational coherences locally at the atomic and molecular scales is, however, much more challenging and in fact has remained elusive so far. Here, we demonstrate that the vibrational coherences induced by broadband laser pulses on a single graphene nanoribbon (GNR) can be probed by femtosecond coherent anti-Stokes Raman spectroscopy (CARS) when performed in a scanning tunnelling microscope (STM). In addition to determining dephasing (~440 fs) and population decay times (~1.8 ps) of the generated phonon wave packets, we are able to track and control the corresponding quantum coherences, which we show to evolve on time scales as short as ~70 fs. We demonstrate that a two-dimensional frequency correlation spectrum unequivocally reveals the quantum couplings between different phonon modes in the GNR.

Accounting for forest condition in Europe based on an international statistical standard.

Covering 35% of Europe's land area, forest ecosystems play a crucial role in safeguarding biodiversity and mitigating climate change. Yet, forest degradation continues to undermine key ecosystem services that forests deliver to society. Here we provide a spatially explicit assessment of the condition of forest ecosystems in Europe following a United Nations global statistical standard on ecosystem accounting, adopted in March 2021. We measure forest condition on a scale from 0 to 1, where 0 represents a degraded ecosystem and 1 represents a reference condition based on primary or protected forests. We show that the condition across 44 forest types averaged 0.566 in 2000 and increased to 0.585 in 2018. Forest productivity and connectivity are comparable to levels observed in undisturbed or least disturbed forests. One third of the forest area was subject to declining condition, signalled by a reduction in soil organic carbon, tree cover density and species richness of threatened birds. Our findings suggest that forest ecosystems will need further restoration, improvements in management and an extended period of recovery to approach natural conditions.

Ultrafast Roaming Mechanisms in Ethanol Probed by Intense Extreme Ultraviolet Free-Electron Laser Radiation: Electron Transfer versus Proton Transfer.

Ultrafast H2+ and H3+ formation from ethanol is studied using pump-probe spectroscopy with an extreme ultraviolet (XUV) free-electron laser. The first pulse creates a dication, triggering H2 roaming that leads to H2+ and H3+ formation, which is disruptively probed by a second pulse. At photon energies of 28 and 32 eV, the ratio of H2+ to H3+ increases with time delay, while it is flat at a photon energy of 70 eV. The delay-dependent effect is ascribed to a competition between electron and proton transfer. High-level quantum chemistry calculations show a flat potential energy surface for H2 formation, indicating that the intermediate state may have a long lifetime. The ab initio molecular dynamics simulation confirms that, in addition to the direct emission, a small portion of H2 undergoes a roaming mechanism that leads to two competing pathways: electron transfer from H2 to C2H4O2+ and proton transfer from C2H4O2+ to H2.

Oblique multi-periscopic prism for field expansion of homonymous hemianopia.

Oblique Fresnel peripheral prisms have been used for field expansion in homonymous hemianopia mobility such as walking and driving. However, limited field expansion, low image quality, and small eye scanning range limit their effectiveness. We developed a new oblique multi-periscopic prism using a cascade of rotated half-penta prisms, which provides 42° horizontal field expansion along with 18° vertical shift, high image quality, and wider eye scanning range. Feasibility and performance of a prototype using 3D-printed module are demonstrated by raytracing, photographic depiction, and Goldmann perimetry with patients with homonymous hemianopia.

Detection of NOTCH1 mutations in paraffin samples in patients with potentially malignant lesions.

Background: On certain occasions, oral cancer is preceded by potentially malignant lesions. The degree of dysplasia in Guinea pigs attempts to determine the risk of developing a malignant lesion. The search for genetic mutations, biomarkers, as a more truthful and reproducible diagnostic tool, tries to fill the gaps in the anatomopathological study. In this line, the present retrospective case-control study is based on the detection of known mutations of the NOTCH1 gene in biopsied samples of potentially malignant lesions from 22 patients who attend the Oral and Maxillofacial Surgery service of the Virgen del Rocío University Hospital. Material and Methods: DNA extraction after dewaxing of the samples using the Minikit QIAamp DNA FFPE tissue extraction kit with extraction kit (reference 56404) of QIAGEN. Subsequently, with the DNA obtained, 4 amplification reactions were carried out using enzyme polymerase. Before sequencing the samples, they were purified with the ExoSAP-IT for PCR product cleaning kit of the INVITROGEN brand. Finally, to detect somatic mutations in NOTCH1, TaqMan Mutation Detection Assays was used and for the analysis of mutations we worked with the Mutation Detector software. Results: The mutation for NOTCH1 is not detected, the studied sample does not present the mutation, or it is below the limits of detection of the software. Conclusions: In the clinical setting of the sample, the NOTCH1 mutation seems to be not very frequent, although NOTCH1 has been described as a gene related to oral cancer in other geographical settings. Key words:Oral cancer, NOTCH1, mutations.

Attosecond photoionization delays in the vicinity of molecular Feshbach resonances.

Temporal delays extracted from photoionization phases are currently determined with attosecond resolution by using interferometric methods. Such methods require special care when photoionization occurs near Feshbach resonances due to the interference between direct ionization and autoionization. Although theory can accurately handle these interferences in atoms, in molecules, it has to face an additional, so far insurmountable problem: Autoionization is slow, and nuclei move substantially while it happens, i.e., electronic and nuclear motions are coupled. Here, we present a theoretical framework to account for this effect and apply it to evaluate time-resolved and vibrationally resolved photoelectron spectra and photoionization phases of N2 irradiated by a combination of an extreme ultraviolet (XUV) attosecond pulse train and an infrared pulse. We show that Feshbach resonances lead to unusual non-Franck-Condon vibrational progressions and to ionization phases that strongly vary with photoelectron energy irrespective of the vibrational state of the remaining molecular cation.

Comparación de Latanoprostene bunod 0,024 % y Latanoprost 0,005 % en glaucoma de ángulo abierto e hipertensión ocular

Introducción: El glaucoma es la principal causa de ceguera irreversible en el mundo. La prevalencia mundial de glaucoma en personas de 40 a 80 años se estima en un 3,5 %. Objetivo: Comparar el efecto reductor de la PIO de Latanoprostene bunod (LBN) al 0,024% con Latanoprost al 0,005 % en sujetos con glaucoma de ángulo abierto (GAA) o hipertensión ocular (HTO). Metodología: Ensayo observacional de estudio de cohorte prospectivo. Resultados: Fue realizado en 28 pacientes (56 ojos) quienes fueron aleatorizados en 2 grupos paralelos (28 ojos por grupo), el grupo Latanoprost y el grupo LBN. En el grupo LBN la media de la PIO antes del tratamiento fue de 25,3 ± 6,6 mmHg y la media de la PIO luego de 1 mes de tratamiento fue de 16,5 ± 4,9 mmHg (p<0,05). En el grupo Latanoprost la media de la PIO antes del tratamiento fue de 23,6 ± 3,6 mmHg y la media de la PIO luego de 1 mes de tratamiento con Latanoprost al 0,005% fue de 15,3 ± 2,4 mmHg (p<0,05). Sin embargo, al comparar las PIOs luego de 1 mes de tratamiento con LBN 0,024% y Latanoprost 0,005% se objetiva que la diferencia en reducción de la presión intraocular entre estos dos fármacos no fue significativa (p= 0,238). Discusión: Las prostaglandinas tópicas, con su potente efecto hipotensor ocular son una importante opción de tratamiento para el glaucoma. La reducción de la PIO es la esperada con ambos medicamentos, sin embargo, no existen diferencias significativas entre ambas luego de 1 mes de uso. Con respecto a los efectos secundarios, en el grupo LBN se encontró más efectos adversos oculares.

Introduction: Glaucoma is the main cause of irreversible blindness worldwide. The global prevalence of glaucoma in people aged 40 to 80 years is estimated at 3.5%. Objective: To compare the intraocular pressure (IOP) lowering effect of 0.024% Latanoprostene bunod (LBN) with 0.005% Latanoprost in subjects with open-angle glaucoma (OAG) or ocular hypertension (OHT). Methods: Observational trial of prospective cohort study. Results: It was performed in 28 patients (56 eyes) who were randomized into 2 parallel groups (28 eyes per group), the Latanoprost group and the Latanoprostene bunod (LBN) group. In the LBN group, the mean intraocular pressure before treatment was 25.3 ± 6.6 mmHg and the mean intraocular pressure after 1 month of treatment was 16.5 ± 4.9 mmHg (p<0,05). In the Latanoprost group, the mean intraocular pressure before treatment was 23.6 ± 3.6 mmHg and the mean intraocular pressure after 1 month of treatment with 0.005% Latanoprost was 15.3 ± 2.4 mmHg (p<0,05). However, when comparing the IOPs to the 1-month treatment with Latanoprostene bunod 0.024% and Latanoprost 0.005%, it is observed, through ANOVA, that the difference in intraocular pressure reduction between these two drugs is not significant (p= 0,238). Discussion: Topical prostaglandins, with their potent ocular hypotensive effect (resulting from increased uveoscleral outflow), are an important treatment option for glaucoma. The IOP reduction is as expected with both drugs, however, there are no significant differences between the two. In the LBN group, more drug-related ocular adverse effects were found after 1 month of use.

Predisposición a la enfermedad neumocócica en la edad pediátrica / Predisposition to Pneumococcal Disease in Pediatric Age

La enfermedad neumocócica invasiva (ENI) es la presentación clínica más severa de la infección confirmada por el aislamiento del S. pneumoniae a partir de un sitio normalmente estéril, como sangre, líquido cefalorraquídeo, líquido pleural y otros líquidos estériles.1,2,3 Las neumonías, sepsis y meningitis engloban 25 por ciento de los 10 millones de fallecidos que ocurren en niños en todo el mundo. El Streptococcus pneumoniae es el agente causal de estas defunciones. La Organización Mundial de la Salud (OMS) estima que, aproximadamente, 800 000 niños fallecen cada año por enfermedad neumocócica, y 90 por ciento de estas defunciones ocurren en países en desarrollo.4 La infección neumocócica presenta un interés creciente por múltiples razones, ya que la morbilidad y mortalidad de las infecciones neumocócicas, tanto localizadas como invasoras, permanecen elevadas a pesar de la antibioterapia. Además, las muertes por infección neumocócica grave ocurren en los primeros 5 días de la enfermedad a pesar del tratamiento y la presencia de más de 90 distintos serotipos de S. pneumoniae, que presentan distinta distribución geográfica, dificulta el desarrollo de una vacuna de aplicación universal. También el elevado y creciente porcentaje de neumococos resistentes a Penicilina y/o a otros antibióticos está planteando importantes problemas terapéuticos.3 Por ello, se hace necesario la identificación de factores de riesgos que predisponen al padecimiento de dicha enfermedad cuya versatilidad de la bacteria S. pneumoniae ha desarrollado diversos mecanismos para evadir la respuesta inmunológica, entre los que destacan las diferencias antigénicas de los polisacáridos capsulares.5 Teniendo en cuenta que, en la mayoría de los casos, los neumococos se transportan en la mucosa del aparato respiratorio superior sin síntomas aparentes, los factores de riesgos que se describen para desarrollar una enfermedad respiratoria constituyen primordial su identificación para actuar sobre la prevención de estos. Hablamos de factores socioeconómicos y sociodemográficos, factores adquiridos del huésped y la predisposición genética del huésped.6 Entre los factores socioeconómicosy sociodemográficos se destacan los hogares con bajos ingresos, donde diversos estudios señalan que hay una mayor incidencia de infección neumocócica, malnutrición y déficit de micronutrientes, prácticas inapropiadas de la lactancia materna y la alimentación, contaminación ambiental (humo del cigarro, combustibles domésticos, otros) y la contaminación atmosférica tras la emisión de gases de fábricas e industrias cercanas al hogar. Y aunque los reportes de la Fondo de las Naciones Unidas para la Infancia (UNICEF) y la OMS no consideran la desnutrición un problema de salud en Cuba; durante las consultas de puericultura es importante evaluar el estado nutricional de los pacientes; debido a que los pacientes desnutridos son muy susceptibles de sufrir infecciones respiratorias agudas, ya que estos niños presentan alteración en la adherencia, quimiotaxis, fagocitosis y en la capacidad microbicida de estas células. Las deficiencias específicas de la cobalamina y el hierro, presentes en estos niños, disminuyen la función de los leucocitos polimorfonucleares de la actividad metabólica asociada a la fagocitosis en macrófagos y disminución de la depuración bacteriana por las células del sistema retículo endotelial. El déficit de estos oligoelementos y otros como cobre, selenio y vitaminas A, E y C también pueden interferir la actividad del sistema de defensa antioxidante y antinfeccioso del pulmón.7 Como riesgo social se identifica el hacinamiento, el nivel cultural alcanzado por la familia al cuidado del infante y; los problemas económicos: las condiciones de la vivienda y el acceso a los servicios de salud y a medicamentos. Otros autores destacan la presencia de animales domésticos.8 De los factores adquiridos del huésped podemos mencionar el bajo peso al nacer, la edad; que es importante señalar que entre más temprano en la vida se presente la infección más riesgo de gravedad presenta el paciente. Se destaca además la presencia...(AU)

Nearly-freestanding supramolecular assembly with tunable structural properties.

The synthesis and design of two-dimensional supramolecular assemblies with specific functionalities is one of the principal goals of the emerging field of molecule-based electronics, which is relevant for many technological applications. Although a large number of molecular assemblies have been already investigated, engineering uniform and highly ordered two-dimensional molecular assemblies is still a challenge. Here we report on a novel approach to prepare wide highly crystalline molecular assemblies with tunable structural properties. We make use of the high-reactivity of the carboxylic acid functional moiety and of the predictable structural features of non-polar alkane chains to synthesize 2D supramolecular assemblies of 4-(decyloxy)benzoic acid (4DBA;C[Formula: see text]H[Formula: see text]O[Formula: see text]) on a Au(111) surface. By means of scanning tunneling microscopy, density functional theory calculations and photoemission spectroscopy, we demonstrate that these molecules form a self-limited highly ordered and defect-free two-dimensional single-layer film of micrometer-size, which exhibits a nearly-freestanding character. We prove that by changing the length of the alkoxy chain it is possible to modify in a controlled way the molecular density of the "floating" overlayer without affecting the molecular assembly. This system is especially suitable for engineering molecular assemblies because it represents one of the few 2D molecular arrays with specific functionality where the structural properties can be tuned in a controlled way, while preserving the molecular pattern.

Circulating levels of mitochondrial oxidative stress-related peptides MOTS-c and Romo1 in stable COPD: A cross-sectional study.

Background: MOTS-c and Romo1 are mitochondrial peptides that are modulated by oxidative stress. No previous studies have explored circulating levels of MOTS-c in patients with chronic obstructive pulmonary disease (COPD). Methods: We enrolled 142 patients with stable COPD and 47 smokers with normal lung function in an observational cross-sectional study. We assessed serum levels of both MOTS-c and Romo1 and associated these findings with clinical characteristics of COPD. Results: Compared with smokers with normal lung function, patients with COPD had lower levels of MOTS-c (p = 0.02) and higher levels of Romo1 (p = 0.01). A multivariate logistic regression analysis revealed that above-median MOTS-c levels were positively associated with Romo1 levels (OR 1.075, 95% CI 1.005-1.150, p = 0.036), but no association was found with other COPD characteristics. Below-median levels of circulating MOTS-c were associated with oxygen desaturation (OR 3.25 95% CI 1.456-8.522, p = 0.005) and walking <350 meters (OR 3.246 95% CI 1.229-8.577, p = 0.018) in six-minute walk test. Above-median levels of Romo1 were positively associated with current smoking (OR 2.756, 95% CI 1.133-6.704, p = 0.025) and negatively associated with baseline oxygen saturation (OR 0.776 95% CI 0.641-0.939, p = 0.009). Conclusions: Reduced levels of circulating MOTS-c and increased levels of Romo1 were detected in patients diagnosed with COPD. Low levels of MOTS-c were associated with oxygen desaturation and poorer exercise capacity using 6 min walk test. Romo1 was associated with current smoking and baseline oxygen saturation. Trial registration: www.clinicaltrials.gov; No.: NCT04449419; URL: www.clinicaltrials.gov. Date of registration: June 26, 2020.

Lipoabdominoplasty: What We Have Implemented and What We Have Modified over 26 Years.

Lipoabdominoplasty is one of the most commonly performed procedures in body-contouring surgery. We present a retrospective study of our 26 years of experience to improve the results and assure the greatest possible safety in lipoabdominoplasty. We include all of our female patients who underwent lipoabdominoplasty performed from July 1996 to June 2022, dividing the patients into two groups: group I underwent circumferential liposuction avoiding abdominal flap liposuction for the first 7 years, and group II underwent circumferential liposuction including abdominal flap liposuction for the subsequent 19 years, pointing out the differences in the processes, results, and complications of both groups. Over a period of 26 years, 973 female patients underwent lipoabdominoplasty: 310 in group I and 663 in group II. Ages were very similar; however, weight, BMI, amount of liposuction material, and weight of the abdominal flap removed were higher in group I. Twenty percent of patients in group I were obese compared to 7% in group II. The average amount of liposuction in group I was 4990 mL compared to 3373 mL in group II and 1120 g of abdominal flap in group I versus 676 g in group II. Minor and major complications were 11.6% and 1.2% in group I versus 9.2% and 0.6% in group II, respectively. In our more than 26 years of performing lipoabdominoplasty, we have maintained most of our initial procedures. These processes have allowed us to perform surgery safely and effectively with a low morbidity rate.

Sustained Cytotoxic Response of Peripheral Blood Mononuclear Cells from Unvaccinated Individuals Admitted to the ICU Due to Critical COVID-19 Is Essential to Avoid a Fatal Outcome.

The main objective of this study was to determine the influence of the cytotoxic activity of peripheral blood mononuclear cells (PBMCs) on the outcome of unvaccinated individuals with critical COVID-19 admitted to the ICU. Blood samples from 23 individuals were collected upon admission and then every 2 weeks for 13 weeks until death (Exitus group) (n = 13) or discharge (Survival group) (n = 10). We did not find significant differences between groups in sociodemographic, clinical, or biochemical data that may influence the fatal outcome. However, direct cellular cytotoxicity of PBMCs from individuals of the Exitus group against pseudotyped SARS-CoV-2-infected Vero E6 cells was significantly reduced upon admission (-2.69-fold; p = 0.0234) and after 4 weeks at the ICU (-5.58-fold; p = 0.0290), in comparison with individuals who survived, and it did not improve during hospitalization. In vitro treatment with IL-15 of these cells did not restore an effective cytotoxicity at any time point until the fatal outcome, and an increased expression of immune exhaustion markers was observed in NKT, CD4+, and CD8+ T cells. However, IL-15 treatment of PBMCs from individuals of the Survival group significantly increased cytotoxicity at Week 4 (6.18-fold; p = 0.0303). Consequently, immunomodulatory treatments that may overcome immune exhaustion and induce sustained, efficient cytotoxic activity could be essential for survival during hospitalization due to critical COVID-19.