Onset of microglial entry into developing quail retina coincides with increased expression of active caspase-3 and is mediated by extracellular ATP and UDP

Microglial cell precursors located in the area of the base of the pecten and the optic nerve head (BP/ONH) start to enter the retina of quail embryos at the 7 th day of incubation (E7), subsequently colonizing the entire retina by central-to-peripheral tangential migration, as previously shown by our group. The present study demonstrates a precise chronological coincidence of the onset of microglial cell entry into the retina with a striking increase in death of retinal cells, as revealed by their active caspase-3 expression and TUNEL staining, in regions dorsal to the BP/ONH area, suggesting that dying retinal cells would contribute to the microglial cell inflow into the retina. However, the molecular mechanisms involved in this inflow are currently unclear. Extracellular nucleotides, such as ATP and UDP, have previously been shown to favor migration of microglia towards brain injuries because they are released by apoptotic cells and stimulate both chemotaxis and chemokinesis in microglial cells via signaling through purinergic receptors. Hence, we tested here the hypothesis that ATP and UDP play a role in the entry and migration of microglial precursors into the developing retina. For this purpose, we used an experimental model system based on organotypic cultures of E6.5 quail embryo retina explants, which mimics the entry and migration of microglial precursors in the in situ developing retina. Inhibition of purinergic signaling by treating retina explants with either apyrase, a nucleotide-hydrolyzing enzyme, or suramin, a broad spectrum antagonist of purinergic receptors, significantly prevents the entry of microglial cells into the retina. In addition, treatment of retina explants with either exogenous ATP or UDP results in significantly increased numbers of microglial cells entering the retina. In light of these findings, we conclude that purinergic signaling by extracellular ATP and UDP is necessary for the entry and migration of microglial cells into the embryonic retina by inducing chemokinesis in these cells

Expression of Inducible Nitric Oxide Synthase (iNOS) in Microglia of the Developing Quail Retina

Inducible nitric oxide synthase (iNOS), which produce large amounts of nitric oxide (NO), is induced in macrophages and microglia in response to inflammatory mediators such as LPS and cytokines. Although iNOS is mainly expressed by microglia that become activated in different pathological and experimental situations, it was recently reported that undifferentiated amoeboid microglia can also express iNOS during normal development. The aim of this study was to investigate the pattern of iNOS expression in microglial cells during normal development and after their activation with LPS by using the quail retina as model. iNOS expression was analyzed by iNOS immunolabeling, western-blot, and RT-PCR. NO production was determined by using DAR-4M AM, a reliable fluorescent indicator of subcellular NO production by iNOS. Embryonic, postnatal, and adult in situ quail retinas were used to analyze the pattern of iNOS expression in microglial cells during normal development. iNOS expression and NO production in LPS-treated microglial cells were investigated by an in vitro approach based on organotypic cultures of E8 retinas, in which microglial cell behavior is similar to that of the in situ retina, as previously demonstrated in our laboratory. We show here that amoeboid microglia in the quail retina express iNOS during normal development. This expression is stronger in microglial cells migrating tangentially in the vitreal part of the retina and is downregulated, albeit maintained, when microglia differentiate and become ramified. LPS treatment of retina explants also induces changes in the morphology of amoeboid microglia compatible with their activation, increasing their lysosomal compartment and upregulating iNOS expression with a concomitant production of NO. Taken together, our findings demonstrate that immature microglial cells express iNOS during normal development, suggesting a certain degree of activation. Furthermore, LPS treatment induces overactivation of amoeboid microglia, resulting in a significant iNOS upregulation.This work was supported by grants from Ministerio de Economía y Competitividad, Spain (BFU2010-19981) and Junta de Andalucía, Spain (P07-CVI-03008)

Modulation of the inflammatory response of immune cells in human peripheral blood by oxidized arachidonoyl aminophospholipids

Aminophospholipids (APL), phosphatidylethanolamine (PE) and phosphatidylserine (PS), can be oxidized upon oxidative stress. Oxidized PE and PS have been detected in clinical samples of different pathologies and may act as modulators of the inflammatory response. However, few studies have focused on the effects of oxidized APL (ox-APL) esterified with arachidonic acid, even though a considerable number of studies have assessed the modulation of the immune system by oxidized 1-palmitoyl-2-arachidonoyl-sn-3-glycerophosphocholine (OxPAPC). In the present study, we have used flow cytometry to evaluate the ability of oxidized PAPE (OxPAPE) and PAPS (OxPAPS) to promote or suppress an inflammatory phenotype on monocytes subsets and myeloid dendritic cells (mDCs). The results indicate that OxPAPE increases the frequency of all monocyte subpopulations expressing TNF-α, which promotes an inflammatory response. However, immune cell stimulation with OxPAPE in the presence of LPS results in a decrease of TNF-α expressed by classical monocytes. Incubation with OxPAPS and LPS induces a decrease in TNF-α produced by monocytes, and a significant decrease in IL-1β expressed by monocytes and mDCs, indicating that OxPAPS reduces the LPS-induced pro-inflammatory expression in these populations. These results show the importance of OxPAPE and OxPAPS as modulators of the inflammatory response and demonstrate their possible contribution to the onset and resolution of human diseases related to oxidative stress and inflammation.publishe

Calidad del sueño en estudiantes universitarios: importancia de la higiene del sueño

Los trastornos del sueño constituyen uno de los problemas de salud más relevantes en las sociedades occidentales. La importancia de una buena calidad de sueño no solamente es fundamental como factor determinante de la salud, sino como elemento propiciador de una buena calidad de vida. La calidad del sueño no se refiere únicamente al hecho de dormir bien durante la noche, sino que también incluye un buen funcionamiento diurno (un adecuado nivel de atención para realizar diferentes tareas). Ello hace que sea fundamental estudiar la incidencia de estos trastornos en distintos tipos de poblaciones, así como los factores que los determinan. Para alcanzar este objetivo, y ante las dificultades que implica la evaluación polisomnográfica en la detección de la calidad de sueño, en la mayoría de los casos se opta por el uso de instrumentos de autoinforme, entre los que destaca el Indice de Calidad del Sueño de Pittsburg. Desde la evaluación conductual consideramos que el sueño está determinado por cuatro diferentes dimensiones: tiempo circadiano, esto es, la hora del día en que se localiza, factores intrínsecos del organismo (edad, sueño, patrones de sueño), conductas facilitadoras e inhibidoras realizadas por el sujeto y el ambiente en que duerme. La higiene del sueño incide sobre estas dos últimas dimensiones, y en nuestro estudio nos centraremos en las conductas inhibidoras (consumo de sustancias psicoactivas). En el estudio se analiza la calidad subjetiva del sueño en una muestra de 716 estudiantes universitarios (584 mujeres y 132 varones) por medio del Indice de Calidad del Sueño de Pittsburg, y se evalúan los efectos del consumo de alcohol, cafeína y tabaco sobre la calidad del sueño. El Indice de Calidad del Sueño de Pittsburg proporciona una puntuación global de la calidad del sueño y puntuaciones parciales en siete componentes distintos: calidad subjetiva del sueño, latencia del sueño, duración del sueño, eficiencia habitual del sueño, alteraciones del sueño, uso de medicación hipnótica y disfunción diurna...Sleep disorders constitute one of the most relevant health problems in Occidental societies. Between 30-40% of the population suffers from insomnia, whereas 1-10% suffers sleep apneas, and around 60% of shift workers report disturbances in the circadian rhythm. The importance of a good sleep quality is not only fundamental in determining health, but is also a propitiatory element for a good quality of life. Sleep quality is not only defined as a good night sleep. It also includes a good daytime functioning (the adequate level of attention needed to complete different tasks). Sleep disorder incidence rates in different populations need to be studied in order to better understand this daytime functioning and its determining factors. To reach this objective, and because of difficulties involved in administering a polysomnographic evaluation to detect sleep quality, self-report measures are used in the majority of the cases (for example, the Pittsburg Sleep Quality Index). From a behavioral evaluation point of view, sleep is made up of four different dimensions: circadian time, that is, the time of day when sleep is located, the organism s intrinsic factors (age, sleep, sleep patterns), a subject s facilitating and inhibiting behaviors, and the environment in which the subject sleeps. As sleep hygiene affects these last two dimensions, in our study we focus on the inhibiting behaviors (psychoactive substance consumption). The present investigation uses the Pittsburg Sleep Quality Index to analyze the subjective sleep quality in a sample of 716 university students (584 females and 132 males). The investigation also evaluates the effects of alcohol, caffeine, and tobacco consumption on sleep quality. The Pittsburg Sleep Quality Index provides a total sleep quality score and partial scores for seven different components: subjective sleep quality; sleep latency; sleep duration; habitual sleep efficiency; sleep dysfunctions; use of hypnotic medication; and daytime dysfunction. The score for each one of the seven components oscillates between zero (absence of difficulty) and three (severe difficulty). The total score ranges from 0 to 21, with a cut-off point of 5, which differentiates between good and bad sleepers. This instrument reveals satisfactory psychometric data in the Spanish population, demonstrating an internal consistency which oscillates between 0.67 in a student sample and 0.81 in a clinical sample. A sensitivity of 88.63% and a specificity of 74.19% is obtained when analyzing the validity..

Asociación entre morfología del pie y rendimiento en gimnasia rítmica

[Abstract] The objectives of the study were to determine the influence of foot morphology on performance in Rhythmic Gymnastics and to analyze the influence of years of practice. The sample consisted of 48 gymnasts who had practiced federated gymnastics and competed during the last year. The results indicate that the gymnasts have predominantly a neutral foot and with a normal footprint, presenting enough asymmetry between feet, not significant, which may be a consequence of asymmetric work and should be corrected in training. Only the range of amplitude of the talocrural joint seems to be a characteristic of foot morphology that affects technical performance and seems more an innate characteristic. The practice of rhythmic gymnastics might not be as decisive a factor as could be supposed in the morphological modifications of the footprint.[Resumen] Los objetivos del estudio fueron determinar la influencia de la morfología del pie en el rendimiento en Gimnasia Rítmica y analizar la influencia de los años de práctica. La muestra estaba compuesta por 48 gimnastas que habían practicado gimnasia federada y competido durante el último año. Los resultados indican que las gimnastas tienen predominantemente un pie neutro y con huella normal, presentando bastante asimetría entre pies, no significativa, lo que puede ser consecuencia de un trabajo asimétrico y debería ser corregido en el entrenamiento. Sólo el rango de amplitud de la articulación talocrural parece ser una característica de la morfología del pie que incida sobre el rendimiento técnico y parece más una característica innata. La práctica de la Gimnasia Rítmica podría no ser un factor tan decisivo como podía suponerse en las modificaciones morfológicas de la huella plantar

SARS-CoV-2 viral RNA detection using the novel CoVradar device associated with the CoVreader smartphone app

Supplementary data to this article can be found online at https://doi. org/10.1016/j.bios.2023.115268The COVID-19 pandemic has highlighted the need for innovative approaches to its diagnosis. Here we present CoVradar, a novel and simple colorimetric method that combines nucleic acid analysis with dynamic chemical labeling (DCL) technology and the Spin-Tube device to detect SARS-CoV-2 RNA in saliva samples. The assay includes a fragmentation step to increase the number of RNA templates for analysis, using abasic peptide nucleic acid probes (DGL probes) immobilized to nylon membranes in a specific dot pattern to capture RNA fragments. Duplexes are formed by labeling complementary RNA fragments with biotinylated SMART bases, which act as templates for DCL. Signals are generated by recognizing biotin with streptavidin alkaline phosphatase and incubating with a chromogenic substrate to produce a blue precipitate. CoVradar results are analysed by CoVreader, a smartphone-based image processing system that can display and interpret the blotch pattern. CoVradar and CoVreader provide a unique molecular assay capable of detecting SARS-CoV-2 viral RNA without the need for extraction, preamplification, or pre-labeling steps, offering advantages in terms of time (similar to 3 h/test), cost (similar to epsilon 1/test manufacturing cost) and simplicity (does not require large equipment). This solution is also promising for developing assays for other infectious diseases.FEDER/Junta de Andalucia-Consejeria de Economia y Conocimiento CV20-77741, A-FQM-760-UGR20, PID 2019-110987RB-I00, PID 2019-103938RB-I00Spanish MCIN/AEI P18-RT-2961, P18-TP-4160FEDER/Junta de Andalucia-Consejeria de Salud y Familias PIP-0232-2021European CommissionMCIN/AEI PTQ 2020-011388, IJC 2020-043307-IEuropean Union NextGenerationEU/PRTR PTQ 2020-011388, IJC 2020-043307-

Electrochemical behavior of hybrid carbon nanomaterials: the chemistry behind electrochemistry

The unzipping of temperature-induced multi-walled carbon nanotubes (MWCNTs) to yield graphene nanoribbons (GNRs) has been studied. These carbon nanomaterials consisting of MWCNTs and unzipped MWCNTs have been synthesized, thoroughly characterized, and subsequently evaluated for electrochemical sensing. Three temperatures (55, 65 and 75 ºC) yielding three carbon nanomaterial termed as GNR-55, GNR-65 and GNR-75, respectively, were carefully studied. Interestingly, GNR-65 became the most suitable material for the electrochemical sensing of a wide range of model analytes displaying the best electrochemical response with independence of the analysed molecule. This electrochemical behaviour seems to be associated to the progress of the unzipping reaction that influences the balance between the Csp2/Csp3 ratio, the graphitic fraction and the type of functional groups introduced. These results revealed the importance of the temperature in the synthesis process, for tailoring carbon nanomaterials which could be used in a particular molecular detection application opening new opportunities for electrochemical sensing applications.This work has been Financial supported by the Spanish Ministry of Science and Innovation (CTQ2011-28135), the NANOAVANSENS program from the Community of Madrid (S2013/MIT-3029), the Spanish MINECO (ENE2013-48816-C5-5-R), the Government Aragon (Project DGA_ESF-T66 CNN) and the European Social Fund (ESF). D. A. M. acknowledges the FPU fellowship from the Ministry of Education, Culture and Sports. D. M. M.-G. acknowledges the fellowship received from the NANOAVANSENS program.Peer reviewe

Effectiveness of mRNA vaccine boosters against infection with the SARS-CoV-2 omicron (B.1.1.529) variant in Spain: a nationwide cohort study

Factor de impacto: 25,71 Q1Background: The omicron (B.1.1.529) variant of SARS-CoV-2 has increased capacity to elude immunity and cause breakthrough infections. The aim of this study was to estimate the effectiveness of mRNA-based vaccine boosters (third dose) against infection with the omicron variant by age, sex, time since complete vaccination, type of primary vaccine, and type of booster. Methods: In this nationwide cohort study, we linked data from three nationwide population registries in Spain (Vaccination Registry, Laboratory Results Registry, and National Health System registry) to select community-dwelling individuals aged 40 years or older, who completed their primary vaccine schedule at least 3 months before the start of follow-up, and had not tested positive for SARS-CoV-2 since the start of the pandemic. On each day between Jan 3, and Feb 6, 2022, we matched individuals who received a booster mRNA vaccine and controls of the same sex, age group, postal code, type of vaccine, time since primary vaccination, and number of previous tests. We estimated risk of laboratory-confirmed SARS-CoV-2 infection using the Kaplan-Meier method and compared groups using risk ratios (RR) and risk differences. Vaccine effectiveness was calculated as one minus RR. Findings: Between Jan 3, and Feb 6, 2022, 3 111 159 matched pairs were included in our study. Overall, the estimated effectiveness from day 7 to 34 after a booster was 51·3% (95% CI 50·2-52·4). Estimated effectiveness was 52·5% (51·3-53·7) for an mRNA-1273 booster and 46·2% (43·5-48·7) for a BNT162b2 booster. Effectiveness was 58·6% (55·5-61·6) if primary vaccination had been with ChAdOx1 nCoV-19 (Oxford-AstraZeneca), 55·3% (52·3-58·2) with mRNA-1273 (Moderna), 49·7% (48·3-51·1) with BNT162b2 (Pfizer-BioNTech), and 48·0% (42·5-53·7) with Ad26.COV2.S (Janssen). Estimated effectiveness was 43·6% (40·0-47·1) when the booster was administered between 151 days and 180 days after complete vaccination and 52·2% (51·0-53·3) if administered more than 180 days after primary scheduled completion. Interpretation: Booster mRNA vaccine-doses were moderately effective in preventing infection with the omicron variant of SARS-CoV-2 for over a month after administration, which indicates their suitability as a strategy to limit the health effects of COVID-19 in periods of omicron variant domination. Estimated effectiveness was higher for mRNA-1273 compared with BNT162b2 and increased with time between completed primary vaccination and booster.S

Real-life outcomes in biotypes of psychotic disorders based on neurocognitive performance

Producción CientíficaAiming at discerning potential biotypes within the psychotic syndrome, we have recently reported the possible existence of two clusters or biotypes across schizophrenia and bipolar disorder characterized by their cognitive performance using the Brief Assessment of Cognition in Schizophrenia (BACS) instrument and validated with independent biological and clinical indexes (Fernández-Linsenbarth et al. in Schizophr Res 229:102–111, 2021). In this previous work, the group with larger cognitive deficits (N = 93, including 69 chronic schizophrenia, 17 first episodes (FE) of schizophrenia and 7 bipolar disorder patients) showed smaller thalamus and hippocampus volume and hyper-synchronic electroencephalogram than the group with milder deficits (N = 105, including 58 chronic schizophrenia, 25 FE and 22 bipolar disorder patients). We predicted that if these biotypes indeed corresponded to different cognitive and biological substrates, their adaptation to real life would be different. To this end, in the present work we have followed up the patients’ population included in that work at 1st and 3rd years after the date of inclusion in the 2021 study and we report on the statistical comparisons of each clinical and real-life outcomes between them. The first cluster, with larger cognitive deficits and more severe biological alterations, showed during that period a decreased capacity for job tenure (1st and 3rd years), more admissions to a psychiatric ward (1st year) and a higher likelihood for quitting psychiatric follow-up (3rd year). Patients in the second cluster, with moderate cognitive deficits, were less compliant with prescribed treatment at the 3rd year. The differences in real-life outcomes may give additional external validity to that yielded by biological measurements to the described biotypes based on neurocognition.Instituto de Salud Carlos III (grant ID PI18/00178)Dirección Regional de Salud de Castilla y León (grant ID GRS 2121/A/2020)Junta de Castilla y León - predoctoral grants from the Consejería de Educación and the European Social Fund (grant IDs VA-183-18 to IFL and VA- 223-19 to RMBRS)Publicación en abierto financiada por el Consorcio de Bibliotecas Universitarias de Castilla y León (BUCLE), con cargo al Programa Operativo 2014ES16RFOP009 FEDER 2014-2020 DE CASTILLA Y LEÓN, Actuación:20007-CL - Apoyo Consorcio BUCL

Effectiveness of mRNA COVID-19 vaccines in preventing SARS-CoV-2 infections and COVID-19 hospitalisations and deaths in elderly long-term care facility residents, Spain, weeks 53 2020 to 13 2021

Residents in long-term care facilities (LTCF) experienced a large morbidity and mortality during the COVID-19 pandemic in Spain and were prioritised for early COVID-19 vaccination. We used the screening method and population-based data sources to obtain estimates of mRNA COVID-19 vaccine effectiveness for elderly LTCF residents. The estimates were 71% (95% CI: 56-82%), 88% (95% CI: 75-95%), and 97% (95% CI: 92-99%), against SARS-CoV-2 infections (symptomatic and asymptomatic), and COVID-19 hospitalisations and deaths, respectively.S