Human gut microbiota analysis of cystic fibrosis infants using metaproteomics.

We report a metaproteomic analysis of the gut microbiota of eight infants with cystic fibrosis, during the first year of life. This is the first study in this disease that uses metaproteomics to analyze stool samples from patients at such a young age.

Evidence for a liquid silicate layer atop the Martian core.

Seismic recordings made during the InSight mission1 suggested that Mars's liquid core would need to be approximately 27% lighter than pure liquid iron2,3, implying a considerable complement of light elements. Core compositions based on seismic and bulk geophysical constraints, however, require larger quantities of the volatile elements hydrogen, carbon and sulfur than those that were cosmochemically available in the likely building blocks of Mars4. Here we show that multiply diffracted P waves along a stratified core-mantle boundary region of Mars in combination with first-principles computations of the thermoelastic properties of liquid iron-rich alloys3 require the presence of a fully molten silicate layer overlying a smaller, denser liquid core. Inverting differential body wave travel time data with particular sensitivity to the core-mantle boundary region suggests a decreased core radius of 1,675 ± 30 km associated with an increased density of 6.65 ± 0.1 g cm-3, relative to previous models2,4-8, while the thickness and density of the molten silicate layer are 150 ± 15 km and 4.05 ± 0.05 g cm-3, respectively. The core properties inferred here reconcile bulk geophysical and cosmochemical requirements, consistent with a core containing 85-91 wt% iron-nickel and 9-15 wt% light elements, chiefly sulfur, carbon, oxygen and hydrogen. The chemical characteristics of a molten silicate layer above the core may be revealed by products of Martian magmatism.

Relación entre el ojo seco y la diabetes mellitus tipo 2

La diabetes mellitus es una patología metabòlica que altera los niveles de glucosa en el cuerpo, siendo más prevalente la tipo 2, la cual puede llegar a modular enfermedades sistémicas que causan diferentes desórdenes metabòlicos y cambios celulares. En cuanto a las alteraciones oftalmológicas, se pueden resaltar la retinopatía diabética y el ojo seco, siendo esta última una condición inflamatoria crónica que ocaciona daños en la superficie ocular. Por lo tanto, esta revisión brindará información de los factores asociados al desarrollo de ojo seco en la diabetes, resaltando cambios en la glicemia y el rol del metabolismo de glucosa sobre estructuras oculares tales como como la glándula lagrimal, glándulas de Meibomio, y en la microvasculatura, que pueden condicionar a trastornos neuropáticos que conducen a la sintomatologia ocular. De igual modo, se describen eventos biológicos como cambios en la expresión epigenética, estrés oxidativo e inflamación que presumiblemente juegan un papel importante en las diabetes y ojo seco, por lo cual la evaluación y análisis de la lágrima en esta población se hace necesaria, teniendo en cuenta los cambios en las estructuras oculares en la diabetes y las novedosas investigaciones sobre biomarcadores de diabetes a través de la película lagrimal.

Diabetes mellitus is a metabolic pathology that alters glucose levels in the body, being type 2 more prevalent, which can lead to modular systemic diseases that cause different metabolic disorders and cellular changes. Regarding ophthalmological alterations, diabetic retinopathy and dry eye can be highlighted, the latter being a chronic inflammatory condition causing damage to the ocular surface. Therefore, this review will provide information on the factors associated with the development of the dry eye in diabetes, highlighting changes in glycemia and the role of glucose metabolism on ocular structures such as the lacrimal gland, Meibomian glands, and the microvasculature, which can condition neuropathic disorders that lead to ocular symptoms, biological events such as changes in epigenetic expression, oxidative stress, and inflammation are prescribed, which presumably play an important role in diabetes and dry eye, for which the evaluation and analysis of tears in this population is done necessary, taking into account the changes in the ocular structures in diabetes and the new research on biomarkers of diabetes through the tear film.

Push out bond strength of hydraulic cements used at different thicknesses.

BACKGROUND: The aim of this study was to compare the pushout bond strength (POBS) of three hydraulic cements, when used at thicknesses of 3 and 5 mm. METHODS: 78 root slices of 3 and 5 mm of thickness were obtained from human teeth. Cylindrical cavities of 1.4 mm of diameter were drilled and filled with Biodentine (BD), Totalfill Root Repair paste (TF) or ProRoot MTA White (PMTA). Pushout tests were performed 21 days later. The fracture pattern of each sample was also analyzed. POBS data were analyzed with Welch and Brown-Forsythe and Tamhane's post hoc tests and a Weibull analysis was also performed. RESULTS: In the 3 mm group, TF showed significantly lower bond strength than BD and PMTA. In the 5 mm group, BD showed significantly higher bond strength than TF. Both BD and TF showed higher bond strength when the thickness of the sample increased, while PMTA did not. CONCLUSIONS: TF and BD achieve higher pushout bond strength resistance when used at a thickness of 5 mm than at 3 mm, while the mean resistance of PMTA is less influenced by the thickness. At 5 mm of thickness, BD and PMTA exhibit similar resistance to displacement. However, the behavior of BD is more predictable than that of its predecessor. BD is a reliable hydraulic cement for clinical situations where thick cavities need to be filled and displacement resistance plays an important role. Clinicians need to consider choosing specific hydraulic cements according to the thickness of material to be used.

Background rates of 41 adverse events of special interest for COVID-19 vaccines in 10 European healthcare databases - an ACCESS cohort study.

BACKGROUND: In May 2020, the ACCESS (The vACCine covid-19 monitoring readinESS) project was launched to prepare real-world monitoring of COVID-19 vaccines. Within this project, this study aimed to generate background incidence rates of 41 adverse events of special interest (AESI) to contextualize potential safety signals detected following administration of COVID-19 vaccines. METHODS: A dynamic cohort study was conducted using a distributed data network of 10 healthcare databases from 7 European countries (Italy, Spain, Denmark, The Netherlands, Germany, France and United Kingdom) over the period 2017 to 2020. A common protocol (EUPAS37273), common data model, and common analytics programs were applied for syntactic, semantic and analytical harmonization. Incidence rates (IR) for each AESI and each database were calculated by age and sex by dividing the number of incident cases by the total person-time at risk. Age-standardized rates were pooled using random effect models according to the provenance of the events. FINDINGS: A total number of 63,456,074 individuals were included in the study, contributing to 211.7 million person-years. A clear age pattern was observed for most AESIs, rates also varied by provenance of disease diagnosis (primary care, specialist care). Thrombosis with thrombocytopenia rates were extremely low ranging from 0.06 to 4.53/100,000 person-years for cerebral venous sinus thrombosis (CVST) with thrombocytopenia (TP) and mixed venous and arterial thrombosis with TP, respectively. INTERPRETATION: Given the nature of the AESIs and the setting (general practitioners or hospital-based databases or both), background rates from databases that show the highest level of completeness (primary care and specialist care) should be preferred, others can be used for sensitivity. The study was designed to ensure representativeness to the European population and generalizability of the background incidence rates. FUNDING: The project has received support from the European Medicines Agency under the Framework service contract nr EMA/2018/28/PE.

Largest recent impact craters on Mars: Orbital imaging and surface seismic co-investigation.

Two >130-meter-diameter impact craters formed on Mars during the later half of 2021. These are the two largest fresh impact craters discovered by the Mars Reconnaissance Orbiter since operations started 16 years ago. The impacts created two of the largest seismic events (magnitudes greater than 4) recorded by InSight during its 3-year mission. The combination of orbital imagery and seismic ground motion enables the investigation of subsurface and atmospheric energy partitioning of the impact process on a planet with a thin atmosphere and the first direct test of martian deep-interior seismic models with known event distances. The impact at 35°N excavated blocks of water ice, which is the lowest latitude at which ice has been directly observed on Mars.

Surface waves and crustal structure on Mars.

We detected surface waves from two meteorite impacts on Mars. By measuring group velocity dispersion along the impact-lander path, we obtained a direct constraint on crustal structure away from the InSight lander. The crust north of the equatorial dichotomy had a shear wave velocity of approximately 3.2 kilometers per second in the 5- to 30-kilometer depth range, with little depth variation. This implies a higher crustal density than inferred beneath the lander, suggesting either compositional differences or reduced porosity in the volcanic areas traversed by the surface waves. The lower velocities and the crustal layering observed beneath the landing site down to a 10-kilometer depth are not a global feature. Structural variations revealed by surface waves hold implications for models of the formation and thickness of the martian crust.

Decoloración coronaria inducida por la utilización de Biodentine y MTA blanco en procedimientos de regeneración pulpar: estudio ex vivo / Coronal discoloration induced by the use of Biodentine and white MTA in pulp regeneration procedures: an ex-vivo study

Se comparó el grado de decoloración de la corona clínica en piezas dentarias anteriores humanas ex-traídas, sometidas a procedimientos de regeneración endodóntica, utilizando MTA blanco o sustituto bioac-tivo de la dentina (Biodentine) como barrera cervical, en presencia de coágulo sanguíneo como andamio. En total se prepararon 24 piezas dentarias anterio-res superiores humanas que fueron divididas en dos grupos control (GC) y dos grupos experimentales (GE). Cada uno incluía 6 piezas dentarias. En los GE se colo-có sangre humana fresca en el interior del conducto, y se confeccionó una barrera de Biodentine (GE3) o MTA (GE4). En los GC se colocó una torunda de algo-dón estéril saturada con solución fisiológica estéril, y se confeccionó una barrera de Biodentine (GC1) o MTA (GC2). El color se evaluó de acuerdo con el espa-cio de color CIE L* a* b* utilizando imágenes fotográfi-cas digitales estandarizadas en dos puntos de tiempo: día 0 (T0) y día 35 (T35). La descripción de los datos in-cluyó mediana (Md), primer cuartil (Q1), tercer cuartil (Q3), media y desviación estándar (DE). Se emplea-ron las pruebas de los rangos con signo de Wilcoxon (RSW) y ANOVA de una vía; p < 0,05 fue considerado significativo. Cuando se comparó ∆E se observaron diferencias significativas entre GC1 y el resto de los materiales (p < 0,05). ∆E fue menor en GC1 (media ± DE; 2,1 ± 1,6) que en los grupos restantes que no pre-sentaron diferencias significativas entre sí. En base a estos resultados, la estabilización del coágulo san-guíneo, como así la limpieza de la cavidad previa a la colocación del Biodentine y el uso de barreras cervi-cales, es imprescindible para evitar la coloración de la corona clínica (AU)

Discoloration remains an unfavorable complication of otherwise successful regenerative endodontic procedure of immature teeth with necrotic pulp. Objective: Compare the degree of discoloration of extracted human teeth after regenerative endodontic procedures, using MTA or Biodentine as a cervical barrier with a blood clot as a scaffold. In total 24 human upper anterior teeth were prepared and divided into two control groups (CG) and two experimental groups (EG). In the EG, fresh human blood was placed inside the root and a Biodentine (GE3) or MTA (GE4) barrier was made in. A sterile cotton swab saturated with sterile physiological solution was placed in the GCs and a Biodentine (GC1) or MTA (GC2) barrier was made in. The color was evaluated according to the CIE L* a* b* color space using standardized digital photographic images at two time points: day 0 (T0) and day 35 (T35). The description of the data included median (Md), first quartile (Q1), third quartile (Q3), means, and standard deviation (SD). Wilcoxon signed rank tests (RSW) and one-way ANOVA were used. p < 0.05 was considered significant. When ∆E was compared, significant differences were observed between GC1 and the rest of the materials (p < 0.05). ∆E was lower in CG1 (mean ± SD; 2.1 ± 1.6) than in the remaining groups, which did not present significant differences between them. There was no significant difference between tooth discolorations with materials in the presence of blood. However, in the absence of blood, Biodentine exhibited less tooth discoloration than MTA (AU)

Effect of marker dosage frequency and spot fecal sampling frequency in the prediction accuracy of fecal output using chromic oxide and titanium dioxide in grazing BON steers.

This study aimed to evaluate the effect of two marker dosage frequencies and two spot fecal sampling frequencies on the variability of fecal output estimation and fecal recovery rate in grazing Blanco Orejinegro (BON) steers with chromium (Cr) or titanium (Ti) as external markers. Four steers (230.5 ± 14.4 kg BW) were used in a 4 × 4 Latin square design in a split-plot arrangement with two markers: Cr or Ti, two marker dosage frequencies: 10.0 g Cr2O3 or TiO2/steer once daily (DF1) or 5.0 g Cr2O3 or TiO2/steer twice daily (DF2), and two fecal sampling frequencies: spot sampling once daily (SF1) or spot sampling twice daily (SF2). Steers were equipped with fecal collection bags to evaluate the actual fecal output (FOR). Fecal marker concentration (FMC) was affected by marker dosage frequency × fecal sampling frequency interaction (P = 0.032): SF1DF1 allowed higher FMC (2.26 g/kg DM) than SF2DF1 (1.95 g/kg DM). Chromium marker allowed higher estimated fecal output (FOe) values when compared to FOR (P < 0.001). Both Ti mean and SD bias (+ 0.074 ± 0.160 kg) were lower than Cr mean and SD bias (+ 0.312 ± 0.272 kg). The Ti fecal output prediction showed lower both RSR (0.586 vs 1.401) and MSPE (0.029 vs 0.167) than Cr prediction. The titanium external marker allowed fecal output estimation with more accuracy in grazing beef cattle trials. A protocol including a once-daily marker dosage associated with a once-daily fecal sampling is plausible, allowing good fecal recovery rates and accurate fecal output estimation.

Phase I dose-escalation single centre clinical trial to evaluate the safety of infusion of memory T cells as adoptive therapy in COVID-19 (RELEASE).

BACKGROUND: Effective treatments are still needed to reduce the severity of symptoms, time of hospitalization, and mortality of COVID-19. SARS-CoV-2 specific memory T-lymphocytes obtained from convalescent donors recovered can be used as passive cell immunotherapy. METHODS: Between September and November 2020 a phase 1, dose-escalation, single centre clinical trial was conducted to evaluate the safety and feasibility of the infusion of CD45RA- memory T cells containing SARS-CoV-2 specific T cells as adoptive cell therapy against moderate/severe cases of COVID-19. Nine participants with pneumonia and/or lymphopenia and with at least one human leukocyte antigen (HLA) match with the donor were infused. The first three subjects received the lowest dose (1 × 105 cells/kg), the next three received the intermediate dose (5 × 105 cells/kg) and the last three received the highest dose (1 × 106 cells/kg) of CD45RA- memory T cells. Clinicaltrials.gov registration: NCT04578210. FINDINGS: All participants' clinical status measured by National Early Warning Score (NEWS) and 7-category point ordinal scales showed improvement six days after infusion. No serious adverse events were reported. Inflammatory parameters were stabilised post-infusion and the participants showed lymphocyte recovery two weeks after the procedure. Donor microchimerism was observed at least for three weeks after infusion in all patients. INTERPRETATION: This study provides preliminary evidence supporting the idea that treatment of COVID-19 patients with moderate/severe symptoms using convalescent CD45RA- memory T cells is feasible and safe. FUNDING: Clinical Trial supported by Spanish Clinical Research Network PT17/0017/0013. Co-funded by European Regional Development Fund/European Social Fund. CRIS CANCER Foundation Grant to AP-M and Agencia Valenciana de Innovación Grant AVI-GVA COVID-19-68 to BS.

The eye: “An organ that must not be forgotten in coronavirus disease 2019 (COVID-2019) pandemic”

The coronavirus family is a group of zoonotic viruses with some recognized reservoirs particularly some bats. A novel coronavirus emerged in the province of Wuhan (China) in December of 2019.The number of infected patient with serious respiratory infection quickly spread around the world to become a global pandemic. The clinical presentation and viral pathogenesis of the coronavirus disease named COVID-19 indicated that the virus is transmitted from person to person through infected droplets entering the respiratory mucosa. Close contact with infected individuals particularly in crowded environments has characterized the rapid spread of the infection.Clinical manifestations of the viral infection have mentioned the presence of some ocular findings such as conjunctival congestion, conjunctivitis and even corneal injury associated with the classical COVID-19 infection. Some animal models of different coronaviruses eye infections have described the viral pathogenesis through tear and conjunctival sampling. On the other hand, we are recommended protective measure to prevent contagion and limit the spread of the virus in health care professionals and contact lenses wearers. (AU)

SARS-CoV-2-Specific Memory T Lymphocytes From COVID-19 Convalescent Donors: Identification, Biobanking, and Large-Scale Production for Adoptive Cell Therapy.

Syndrome coronavirus 2 (SARS-CoV-2) pandemic is causing a second outbreak significantly delaying the hope for the virus' complete eradication. In the absence of effective vaccines, we need effective treatments with low adverse effects that can treat hospitalized patients with COVID-19 disease. In this study, we determined the existence of SARS-CoV-2-specific T cells within CD45RA- memory T cells in the blood of convalescent donors. Memory T cells can respond quickly to infection and provide long-term immune protection to reduce the severity of COVID-19 symptoms. Also, CD45RA- memory T cells confer protection from other pathogens encountered by the donors throughout their life. It is of vital importance to resolve other secondary infections that usually develop in patients hospitalized with COVID-19. We found SARS-CoV-2-specific memory T cells in all of the CD45RA- subsets (CD3+, CD4+, and CD8+) and in the central memory and effector memory subpopulations. The procedure for obtaining these cells is feasible, easy to implement for small-scale manufacture, quick and cost-effective, involves minimal manipulation, and has no GMP requirements. This biobank of specific SARS-CoV-2 memory T cells would be immediately available "off-the-shelf" to treat moderate/severe cases of COVID-19, thereby increasing the therapeutic options available for these patients.