Oral microbial dysbiosis in cardiovascular diseases

The most common diseases in humans are oral infections. Although modern research is mainly concerned with the role of the gut microbiota in systemic diseases, there are also reports indicating that oral infections, and especially periodontal infection, are one of the risk factors for atherosclerotic cardiovascular disease (CVD).The composition of the oral biofilm is a community of several hundred species of bacteria, fungi, spirochetes, viruses and protozoa. It varies depending on the state of health and disease. Pathogenic bacteria in the oral cavity can cause systemic disease by entering the bloodstream or by triggering immune responses at the cellular level. The discovery of the role of the oral microbiome in CVD is leading to new methods of prevention and their treatment.  In this review, we discuss  the various mechanisms by which oral dysbiosis may contribute to the pathogenesis of CVD as well as available options for their prevention and treatment. Oral dysbiosis, or the imbalance of bacteria in the oral cavity, has been linked to an increased risk of CVD. Several mechanisms have been proposed to explain how oral dysbiosis may contribute to CVD, including: The production of inflammatory molecules by oral bacteria. The activation of the immune system, which can lead to inflammation throughout the body. The entry of oral bacteria into the bloodstream, where they can travel to other organs and tissues. There are a number of things that can be done to prevent oral dysbiosis and reduce the risk of CVD, including: Good oral hygiene, such as brushing and flossing twice a day. Regular dental checkups and cleanings. Avoiding tobacco use. Eating a healthy diet. Conclusions. The evidence is growing that oral dysbiosis is a risk factor for CVD. Further research is needed to better understand the mechanisms involved and to develop effective interventions for prevention and treatment. The following are some other important points: The role of oral dysbiosis in CVD is likely to be complex and involve multiple factors. The effects of oral dysbiosis on CVD may vary depending on the individual's overall health status and other risk factors. More research is needed to determine the optimal methods for preventing and treating oral dysbiosis in order to reduce the risk of CVD

Intestinal dysbiosis in heart failure - modulation of dysbiosis as a potential therapeutic target

The last decade has provided extensive information on the human gut microbiota. The microorganisms populating the gastrointestinal tract play important roles in maintaining the body's homeostasis. It turns out that the intestinal microbiota can affect many diseases from various branches of medicine. The importance of the function of the microflora can also affect cardiovascular diseases (CVD), including heart failure (HF). The microflora influences among other things, nutrient digestion, vitamin production or the production of bioactive metabolites including trimethylamine/trimethylamine N-oxide, short-chain fatty acids and bile acids. Therefore, changes in the composition of the intestinal microflora, defined as dysbiosis, have become one of the key pathogenic factors in many diseases. There is emerging evidence of a strong correlation between gut microflora and the occurrence of cardiovascular disease. In patients with cardiovascular disease and corresponding risk factors, the composition and proportions of the intestinal microflora differed significantly from healthy subjects. Differences in microbial composition and marked fluctuations in the levels of biomarkers such as TMAO, zonulin, LPS, SCFAs may become helpful in the diagnosis of cardiovascular diseases. For this reason, the intestinal microflora and its metabolic pathways have recently become the subject of numerous studies. A very important issue is the fact that it is possible to regulate the intestinal microflora through diet, the use of prebiotics, probiotics or influence through a much larger intervention - for example, fecal mass transplantation. These possibilities have become new strategies in the treatment of HF. The main purpose of this review is to summarize recent studies that illustrate the complex interactions between the microbiome and the occurrence of HF. Conclusions. The gut microbiota is a complex ecosystem of microorganisms that live in the human gut. The gut microbiota plays an important role in maintaining the body's health, including the cardiovascular system. Dysbiosis, or an imbalance in the gut microbiota, has been linked to the development of heart failure. Gut microbiota metabolites, such as trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFAs), and bile acids, can have harmful effects on the heart. Diet, probiotics, and fecal microbiota transplantation (FMT) are all potential interventions for improving gut microbiota and reducing the risk of heart failure. More research is needed to fully understand the role of gut microbiota in heart failure and to develop effective treatment strategies

SCN1A overexpression, associated with a genomic region marked by a risk variant for a common epilepsy, raises seizure susceptibility

Mesial temporal lobe epilepsy with hippocampal sclerosis and a history of febrile seizures is associated with common variation at rs7587026, located in the promoter region of SCN1A. We sought to explore possible underlying mechanisms. SCN1A expression was analysed in hippocampal biopsy specimens of individuals with mesial temporal lobe epilepsy with hippocampal sclerosis who underwent surgical treatment, and hippocampal neuronal cell loss was quantitatively assessed using immunohistochemistry. In healthy individuals, hippocampal volume was measured using MRI. Analyses were performed stratified by rs7587026 type. To study the functional consequences of increased SCN1A expression, we generated, using transposon-mediated bacterial artificial chromosome transgenesis, a zebrafish line expressing exogenous scn1a, and performed EEG analysis on larval optic tecta at 4 day post-fertilization. Finally, we used an in vitro promoter analysis to study whether the genetic motif containing rs7587026 influences promoter activity. Hippocampal SCN1A expression differed by rs7587026 genotype (Kruskal-Wallis test P = 0.004). Individuals homozygous for the minor allele showed significantly increased expression compared to those homozygous for the major allele (Dunn's test P = 0.003), and to heterozygotes (Dunn's test P = 0.035). No statistically significant differences in hippocampal neuronal cell loss were observed between the three genotypes. Among 597 healthy participants, individuals homozygous for the minor allele at rs7587026 displayed significantly reduced mean hippocampal volume compared to major allele homozygotes (Cohen's D = - 0.28, P = 0.02), and to heterozygotes (Cohen's D = - 0.36, P = 0.009). Compared to wild type, scn1lab-overexpressing zebrafish larvae exhibited more frequent spontaneous seizures [one-way ANOVA F(4,54) = 6.95 (P < 0.001)]. The number of EEG discharges correlated with the level of scn1lab overexpression [one-way ANOVA F(4,15) = 10.75 (P < 0.001]. Finally, we showed that a 50 bp promoter motif containing rs7587026 exerts a strong regulatory role on SCN1A expression, though we could not directly link this to rs7587026 itself. Our results develop the mechanistic link between rs7587026 and mesial temporal lobe epilepsy with hippocampal sclerosis and a history of febrile seizures. Furthermore, we propose that quantitative precision may be important when increasing SCN1A expression in current strategies aiming to treat seizures in conditions involving SCN1A haploinsufficiency, such as Dravet syndrome

Magnetic fields inferred by Solar Orbiter: A comparison between SO/PHI-HRT and SDO/HMI

Context. The High Resolution Telescope (HRT) of the Polarimetric and Helioseismic Imager on board the Solar Orbiter spacecraft (SO/PHI) and the Helioseismic and Magnetic Imager (HMI) on board the Solar Dynamics Observatory (SDO) both infer the photospheric magnetic field from polarised light images. SO/PHI is the first magnetograph to move out of the Sun–Earth line and will provide unprecedented access to the Sun’s poles. This provides excellent opportunities for new research wherein the magnetic field maps from both instruments are used simultaneously. Aims. We aim to compare the magnetic field maps from these two instruments and discuss any possible differences between them. Methods. We used data from both instruments obtained during Solar Orbiter’s inferior conjunction on 7 March 2022. The HRT data were additionally treated for geometric distortion and degraded to the same resolution as HMI. The HMI data were re-projected to correct for the 3° separation between the two observatories. Results. SO/PHI-HRT and HMI produce remarkably similar line-of-sight magnetograms, with a slope coefficient of 0.97, an offset below 1 G, and a Pearson correlation coefficient of 0.97. However, SO/PHI-HRT infers weaker line-of-sight fields for the strongest fields. As for the vector magnetic field, SO/PHI-HRT was compared to both the 720-second and 90-second HMI vector magnetic field: SO/PHI-HRT has a closer alignment with the 90-second HMI vector. In the weak signal regime (< 600 G), SO/PHI-HRT measures stronger and more horizontal fields than HMI, very likely due to the greater noise in the SO/PHI-HRT data. In the strong field regime (≳600 G), HRT infers lower field strengths but with similar inclinations (a slope of 0.92) and azimuths (a slope of 1.02). The slope values are from the comparison with the HMI 90-second vector. Possible reasons for the differences found between SO/PHI-HRT and HMI magnetic field parameters are discussed.Sección Deptal. de Óptica (Óptica)Fac. de Óptica y OptometríaTRUEBMWi - Bundesministerium für Wirtschaft und Energie (Alemania)AEI/MCIN/10.13039/501100011033Ministerio de ciencia e innovación de EspañaInstituto Astrofísico de Andalucía (España)Agencia Estatal de Investigación (España)Fondo Europeo de Desarrollo Regional (Fondos FEDER)Centre national d'études spatiales (CNES) (Francia)CSIC (Centro Superior de Investigaciones Científicas) (España)pu

Novel application of [18F]DPA714 for visualizing the pulmonary inflammation process of SARS-CoV-2-infection in rhesus monkeys (Macaca mulatta)

RATIONALE: The aim of this study was to investigate the application of [18F]DPA714 to visualize the inflammation process in the lungs of SARS-CoV-2-infected rhesus monkeys, focusing on the presence of pulmonary lesions, activation of mediastinal lymph nodes and surrounded lung tissue. METHODS: Four experimentally SARS-CoV-2 infected rhesus monkeys were followed for seven weeks post infection (pi) with a weekly PET-CT using [18F]DPA714. Two PET images, 10 min each, of a single field-of-view covering the chest area, were obtained 10 and 30 min after injection. To determine the infection process swabs, blood and bronchoalveolar lavages (BALs) were obtained. RESULTS: All animals were positive for SARS-CoV-2 in both the swabs and BALs on multiple timepoints pi. The initial development of pulmonary lesions was already detected at the first scan, performed 2-days pi. PET revealed an increased tracer uptake in the pulmonary lesions and mediastinal lymph nodes of all animals from the first scan obtained after infection and onwards. However, also an increased uptake was detected in the lung tissue surrounding the lesions, which persisted until day 30 and then subsided by day 37-44 pi. In parallel, a similar pattern of increased expression of activation markers was observed on dendritic cells in blood. PRINCIPAL CONCLUSIONS: This study illustrates that [18F]DPA714 is a valuable radiotracer to visualize SARS-CoV-2-associated pulmonary inflammation, which coincided with activation of dendritic cells in blood. [18F]DPA714 thus has the potential to be of added value as diagnostic tracer for other viral respiratory infections

Longitudinal positron emission tomography and postmortem analysis reveals widespread neuroinflammation in SARS-CoV-2 infected rhesus macaques

BACKGROUND: Coronavirus disease 2019 (COVID-19) patients initially develop respiratory symptoms, but they may also suffer from neurological symptoms. People with long-lasting effects after acute infections with severe respiratory syndrome coronavirus 2 (SARS-CoV-2), i.e., post-COVID syndrome or long COVID, may experience a variety of neurological manifestations. Although we do not fully understand how SARS-CoV-2 affects the brain, neuroinflammation likely plays a role. METHODS: To investigate neuroinflammatory processes longitudinally after SARS-CoV-2 infection, four experimentally SARS-CoV-2 infected rhesus macaques were monitored for 7 weeks with 18-kDa translocator protein (TSPO) positron emission tomography (PET) using [18F]DPA714, together with computed tomography (CT). The baseline scan was compared to weekly PET-CTs obtained post-infection (pi). Brain tissue was collected following euthanasia (50 days pi) to correlate the PET signal with TSPO expression, and glial and endothelial cell markers. Expression of these markers was compared to brain tissue from uninfected animals of comparable age, allowing the examination of the contribution of these cells to the neuroinflammatory response following SARS-CoV-2 infection. RESULTS: TSPO PET revealed an increased tracer uptake throughout the brain of all infected animals already from the first scan obtained post-infection (day 2), which increased to approximately twofold until day 30 pi. Postmortem immunohistochemical analysis of the hippocampus and pons showed TSPO expression in cells expressing ionized calcium-binding adaptor molecule 1 (IBA1), glial fibrillary acidic protein (GFAP), and collagen IV. In the hippocampus of SARS-CoV-2 infected animals the TSPO+ area and number of TSPO+ cells were significantly increased compared to control animals. This increase was not cell type specific, since both the number of IBA1+TSPO+ and GFAP+TSPO+ cells was increased, as well as the TSPO+ area within collagen IV+ blood vessels. CONCLUSIONS: This study manifests [18F]DPA714 as a powerful radiotracer to visualize SARS-CoV-2 induced neuroinflammation. The increased uptake of [18F]DPA714 over time implies an active neuroinflammatory response following SARS-CoV-2 infection. This inflammatory signal coincides with an increased number of TSPO expressing cells, including glial and endothelial cells, suggesting neuroinflammation and vascular dysregulation. These results demonstrate the long-term neuroinflammatory response following a mild SARS-CoV-2 infection, which potentially precedes long-lasting neurological symptoms

Autonomous on-board data processing and instrument calibration software for the Polarimetric and Helioseismic Imager on-board the Solar Orbiter mission

This is an open access article. Published by SPIE under a Creative Commons Attribution 4.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.A frequent problem arising for deep space missions is the discrepancy between the amount of data desired to be transmitted to the ground and the available telemetry bandwidth. A part of these data consists of scientific observations, being complemented by calibration data to help remove instrumental effects. We present our solution for this discrepancy, implemented for the Polarimetric and Helioseismic Imager on-board the Solar Orbiter mission, the first solar spectropolarimeter in deep space. We implemented an on-board data reduction system that processes calibration data, applies them to the raw science observables, and derives science-ready physical parameters. This process reduces the raw data for a single measurement from 24 images to five, thus reducing the amount of downlinked data, and in addition, renders the transmission of the calibration data unnecessary. Both these on-board actions are completed autonomously. © The Authors. Published by SPIE under a Creative Commons Attribution 4.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.This work was carried out in the framework of the International Max Planck Research School for Solar System Science at the Max Planck Institute for Solar System Research. Solar Orbiter is a mission led by the European Space Agency with contribution from the National Aeronautics and Space Administration (NASA). The Polarimetric and Helioseismic Imager instrument is supported by the German Aerospace Center (DLR) under grant Nos. 50 OT 1201 and 50 OT 1901. The Spanish contribution has been partly funded by the Spanish Research Agency under projects under grant Nos. ESP2016-77548-C5 and RTI2018-096886-B-C5, partially including European FEDER funds. IAA-CSIC members acknowledge and funds from the Spanish Ministry of Science and Innovation “Centro de Excelencia Severo Ochoa” Program under grant No. SEV-2017-0709. The solar data used in the tests are the courtesy of NASA/SDO HMI science team. Parts of the work shown in this paper have been introduced at the SPIE Astronomical Telescopes + Instrumentation conference.42 EditorialPeer reviewe

Slow Solar Wind Connection Science during Solar Orbiter’s First Close Perihelion Passage

The Slow Solar Wind Connection Solar Orbiter Observing Plan (Slow Wind SOOP) was developed to utilize the extensive suite of remote-sensing and in situ instruments on board the ESA/NASA Solar Orbiter mission to answer significant outstanding questions regarding the origin and formation of the slow solar wind. The Slow Wind SOOP was designed to link remote-sensing and in situ measurements of slow wind originating at open–closed magnetic field boundaries. The SOOP ran just prior to Solar Orbiter’s first close perihelion passage during two remote-sensing windows (RSW1 and RSW2) between 2022 March 3–6 and 2022 March 17–22, while Solar Orbiter was at respective heliocentric distances of 0.55–0.51 and 0.38–0.34 au from the Sun. Coordinated observation campaigns were also conducted by Hinode and IRIS. The magnetic connectivity tool was used, along with low-latency in situ data and full-disk remote-sensing observations, to guide the target pointing of Solar Orbiter. Solar Orbiter targeted an active region complex during RSW1, the boundary of a coronal hole, and the periphery of a decayed active region during RSW2. Postobservation analysis using the magnetic connectivity tool, along with in situ measurements from MAG and SWA/PAS, showed that slow solar wind originating from two out of three of the target regions arrived at the spacecraft with velocities between ∼210 and 600 km s−1. The Slow Wind SOOP, despite presenting many challenges, was very successful, providing a blueprint for planning future observation campaigns that rely on the magnetic connectivity of Solar Orbiter