Assistance Device Based on SSVEP-BCI Online to Control a 6-DOF Robotic Arm.

This paper explores the potential benefits of integrating a brain-computer interface (BCI) utilizing the visual-evoked potential paradigm (SSVEP) with a six-degrees-of-freedom (6-DOF) robotic arm to enhance rehabilitation tools. The SSVEP-BCI employs electroencephalography (EEG) as a method of measuring neural responses inside the occipital lobe in reaction to pre-established visual stimulus frequencies. The BCI offline and online studies yielded accuracy rates of 75% and 83%, respectively, indicating the efficacy of the system in accurately detecting and capturing user intent. The robotic arm achieves planar motion by utilizing a total of five control frequencies. The results of this experiment exhibited a high level of precision and consistency, as indicated by the recorded values of ±0.85 and ±1.49 cm for accuracy and repeatability, respectively. Moreover, during the performance tests conducted with the task of constructing a square within each plane, the system demonstrated accuracy of 79% and 83%. The use of SSVEP-BCI and a robotic arm together shows promise and sets a solid foundation for the development of assistive technologies that aim to improve the health of people with amyotrophic lateral sclerosis, spina bifida, and other related diseases.

Nature-based solutions for coastal protection in sheltered and exposed coastal waters: integrated monitoring program for baseline ecological structure and functioning assessment.

Nature-based solutions, such as shellfish reefs, can support natural coastal defence and be a potential solution for climate-resilient shorelines in the future. In the Belgian Part of the North Sea, the "Coastbusters" projects aim to develop nature-based coastal protection by favouring subtidal mussel bed establishment on the seafloor through typical longline aquaculture techniques. Mussel beds are dependent on environmental conditions, and both influence the physical and biogeochemical features in a soft-sediment environment. Therefore, a comprehensive ecological monitoring program is essential to assess the success of future mussel bed development and its influence on the surrounding ecosystem. For establishing a monitoring baseline of the two experimental areas, a combination of conventional benthic assessment methods (grab sampling and granulometry) and non-invasive techniques (sediment profile imaging and transect diving video surveys) were utilised. Although mussel reefs did not yet develop by the time of this study, clear differences in ecological and sedimentological characteristics were found between two experimental areas (sheltered and exposed), subjected to slightly different hydrodynamic conditions. The one sheltered by coastal sandbanks was dominated by fine-muddy sand, higher species richness, biomass, and higher biological activity (burrows, fauna, and biological beds) as observed by all methods in one or another way. Moreover, functional diversity indices revealed a higher partitioning of the total available resources, suggesting more complex ecological processes in the sheltered area. Conversely, the area more exposed to the open sea was dominated by more sandy sediments, and fewer organisms were found. The combination of those different monitoring tools provides an integrated, complementary view, from different perspectives, on the biological, physical and functional characteristics of the study areas.

Deeply 3D-T1-TFE hypointense voxels are characteristic of phase-rim lesions in multiple sclerosis.

OBJECTIVES: The development of new drugs for the treatment of progressive multiple sclerosis (MS) highlights the need for new prognostic biomarkers. Phase-rim lesions (PRLs) have been proposed as markers of progressive disease but are difficult to identify and quantify. Previous studies have identified T1-hypointensity in PRLs. The aim of this study was to compare the intensity profiles of PRLs and non-PRL white-matter lesions (nPR-WMLs) on three-dimensional T1-weighted turbo field echo (3DT1TFE) MRI. We then evaluated the performance of a derived metric as a surrogate for PRLs as potential markers for risk of disease progression. METHODS: This study enrolled a cohort of relapsing-remitting (n = 10) and secondary progressive MS (n = 10) patients for whom 3 T MRI was available. PRLs and nPR-WMLs were segmented, and voxel-wise normalized T1-intensity histograms were analyzed. The lesions were divided equally into training and test datasets, and the fifth-percentile (p5)-normalized T1-intensity of each lesion was compared between groups and used for classification prediction. RESULTS: Voxel-wise histogram analysis showed a unimodal histogram for nPR-WMLs and a bimodal histogram for PRLs with a large peak in the hypointense limit. Lesion-wise analysis included 1075 nPR-WMLs and 39 PRLs. The p5 intensity of PRLs was significantly lower than that of nPR-WMLs. The T1 intensity-based PRL classifier had a sensitivity of 0.526 and specificity of 0.959. CONCLUSIONS: Profound hypointensity on 3DT1TFE MRI is characteristic of PRLs and rare in other white-matter lesions. Given the widespread availability of T1-weighted imaging, this feature might serve as a surrogate biomarker for smoldering inflammation. CLINICAL RELEVANCE STATEMENT: Quantitative analysis of 3DT1TFE may detect deeply hypointense voxels in multiple sclerosis lesions, which are highly specific to PRLs. This could serve as a specific indicator of smoldering inflammation in MS, aiding in early detection of disease progression. KEY POINTS: • Phase-rim lesions (PRLs) in multiple sclerosis present a characteristic T1-hypointensity on 3DT1TFE MRI. • Intensity-normalized 3DT1TFE can be used to systematically identify and quantify these deeply hypointense foci. • Deep T1-hypointensity may act as an easily detectable, surrogate marker for PRLs.

Monte Carlo model of a prototype flat-panel detector for multi-energy applications in radiotherapy.

BACKGROUND: The incorporation of multi-energy capabilities into radiotherapy flat-panel detectors offers advantages including enhanced soft tissue visualization by reduction of signal from overlapping anatomy such as bone in 2D image projections; creation of virtual monoenergetic images for 3D contrast enhancement, metal artefact reduction and direct acquisition of relative electron density. A novel dual-layer on-board imager offering dual energy processing capabilities is being designed. As opposed to other dual-energy implementation techniques which require separate acquisition with two different x-ray spectra, the dual-layer detector design enables simultaneous acquisition of high and low energy images with a single exposure. A computational framework is required to optimize the design parameters and evaluate detector performance for specific clinical applications. PURPOSE: In this study, we report on the development of a Monte Carlo (MC) model of the imager including model validation. METHODS: The stack-up of the dual-layer imager (DLI) was implemented in GEANT4 Application for Tomographic Emission (GATE). The DLI model has an active area of 43×43 cm2 , with top and bottom Cesium Iodide (CsI) scintillators of 600 and 800 µm thickness, respectively. Measurement of spatial resolution and imaging of dedicated multi-material dual-energy (DE) phantoms were used to validate the model. The modulation transfer function (MTF) of the detector was calculated for a 120 kVp x-ray spectrum using a 0.5 mm thick tantalum edge rotated by 2.5o . For imaging validation, the DE phantom was imaged using a 140 kVp x-ray spectrum. For both validation simulations, corresponding measurements were done using an initial prototype of the imager. Agreement between simulations and measurement was assessed using normalized root mean square error (NRMSE) and 1D profile difference for the MTF and phantom images respectively. Further comparison between measurement and simulation was made using virtual monoenergetic images (VMIs) generated from basis material images derived using precomputed look-up tables. RESULTS: The MTF of the bottom layer of the dual-layer model shows values decreasing more quickly with spatial frequency, compared to the top layer, due to the thicker bottom scintillator thickness and scatter from the top layer. A comparison with measurement shows NRMSE of 0.013 and 0.015 as well as identical MTF50 of 0.8 mm1 and 1.0 mm1 for the top and bottom layer respectively. For the DE imaging of the DE-phantom, although a maximum deviation of 3.3% is observed for the 10 mm aluminum and Teflon inserts at the top layer, the agreement for all other inserts is less than 2.2% of the measured value at both layers. Material decomposition of simulated scatter-free DE images gives an average accuracy in PMMA and aluminum composition of 4.9% and 10.3% for 11-30 mm PMMA and 1-10 mm aluminum objects respectively. A comparison of decomposed values using scatter containing measured and simulated DE images shows good agreement within statistical uncertainty. CONCLUSION: Validation using both MTF and phantom imaging shows good agreement between simulation and measurements. With the present configuration of the digital prototype, the model can generate material decomposed images and virtual monoenergetic images.

A selective nonpeptide somatostatin receptor 5 agonist effectively decreases insulin secretion in hyperinsulinism.

Congenital hyperinsulinism (HI), a beta cell disorder most commonly caused by inactivating mutations of beta cell KATP channels, results in dysregulated insulin secretion and persistent hypoglycemia. Children with KATP-HI are unresponsive to diazoxide, the only FDA-approved drug for HI, and utility of octreotide, the second-line therapy, is limited because of poor efficacy, desensitization, and somatostatin receptor type 2 (SST2)-mediated side effects. Selective targeting of SST5, an SST receptor associated with potent insulin secretion suppression, presents a new avenue for HI therapy. Here, we determined that CRN02481, a highly selective nonpeptide SST5 agonist, significantly decreased basal and amino acid-stimulated insulin secretion in both Sur1-/- (a model for KATP-HI) and wild-type mouse islets. Oral administration of CRN02481 significantly increased fasting glucose and prevented fasting hypoglycemia compared to vehicle in Sur1-/- mice. During a glucose tolerance test, CRN02481 significantly increased glucose excursion in both WT and Sur1-/- mice compared to the control. CRN02481 also reduced glucose- and tolbutamide-stimulated insulin secretion from healthy, control human islets similar to the effects observed with SS14 and peptide somatostatin analogs. Moreover, CRN02481 significantly decreased glucose- and amino acid-stimulated insulin secretion in islets from two infants with KATP-HI and one with Beckwith-Weideman Syndrome-HI. Taken together, these data demonstrate that a potent and selective SST5 agonist effectively prevents fasting hypoglycemia and suppresses insulin secretion not only in a KATP-HI mouse model but also in healthy human islets and islets from HI patients.

The age at onset of relapsing-remitting multiple sclerosis has increased over the last five decades.

BACKGROUND: Patients with relapsing-remitting multiple sclerosis (RRMS) most commonly experience their first symptoms between 20 and 40 years of age. The objective of this study was to investigate how the age at which the first symptoms of RRMS occur has changed over the past decades. METHODS: Patients who were followed up in our unit after an initial diagnosis of RRMS using the Poser or McDonald criteria and who experienced their first symptoms between January 1970 and December 2019 were included in the study. The cohort was divided into five groups according to the decade in which the first symptoms appeared. The age at disease onset was compared across decades. Changes in age were also determined after excluding patients with early-onset disease (<18 years of age) and those with late-onset disease (>50 years of age) to avoid bias. RESULTS: The cohort included 1,622 patients with RRMS, 67.6% of whom were women. Among them, 5.9% and 4% had early-onset and late-onset disease, respectively. The mean age ± standard deviation at onset was 31.11 ± 9.82 years, with no differences between men and women. The mean ages at onset were 23.79 ± 10.19 years between 1970 and 1979, 27.86 ± 9.22 years between 1980 and 1989, 30.07 ± 9.32 years between 1990 and 1999, 32.12 ± 9.47 between 2000 and 2009, and 34.28 ± 9.83 years between 2010 and 2019. The ages at disease onset were progressively higher in the later decades; this trend was statistically significant (p < 0.001), with a Pearson linear correlation coefficient R of 0.264 and R2 of 0.070 (p < 0.001). The results were similar when analysing men and women separately. We conducted an analysis of 1,460 patients (mean age at onset: 31.10 ± 7.99 years), after excluding patients with early-onset and late-onset disease. In this specific subgroup, the mean ages at disease onset were 28.38 ± 8.17 years between 1970 and 1979, 29.22 ± 7.51 years between 1980 and 1989, 30.06 ± 8.02 years between 1990 and 1999, 31.46 ± 7.77 years between 2000 and 2009, and 33.37 ± 7.97 years between 2010 and 2019. The trend was also statistically significant (p < 0.001), with a Pearson linear correlation coefficient R of 0.193 and R2 of 0.037 (p < 0.001). CONCLUSION: Our data showed that the age at RRMS onset has increased over the past decades.

Charge Effects on the Photodegradation of Single Optically Trapped Oleic Acid Aerosol Droplets.

It has recently been reported that reactions can occur faster in microdroplets than in extended condensed matter. The electric charge of droplets has also been suggested as a possible cause of this phenomenon. Here, we investigate the influence of electric charges on the photodegradation of single, optically trapped oleic acid aerosol droplets in the absence of other reactive species. The temporal evolution of the chemical composition and the size of droplets with charge states ranging from 0 to 104 elementary charges were retrieved from Raman spectra and elastic light scattering, respectively. No influence of the droplet charge was observed, either on the chemical composition or on the kinetics. Based on a kinetic multilayer model, we propose a reaction mechanism with the photoexcitation of oleic acid into an excited state, subsequent decay into intermediates and further photoexcitation of intermediates and their decay into nonvolatile and volatile products.

Surface solvation of Martian salt analogues at low relative humidities.

Salt aerosols play important roles in many processes related to atmospheric chemistry and the climate systems on both Earth and Mars. Complicated and still poorly understood processes occur on the salt surfaces when interacting with water vapor. In this study, ambient pressure X-ray photoelectron spectroscopy (APXPS) is used to characterize the surface chemical environment of Martian salt analogues originating from saline lakes and playas, as well as their responses to varying relative humidities. Generally, APXPS shows similar ionic compositions to those observed by ion chromatography (IC). However, XPS is a surface-sensitive method while IC is bulk-sensitive and differences are observed for species that preferentially partition to the surface or the bulk. Element-selective surface enhancement of Cl- is observed, likely caused by the presence of SO4 2-. In addition, Mg2+ is concentrated on the surface while Na+ is relatively depleted in the surface layer. Hence, the cations (Na+ and Mg2+) and the anions (Cl- and SO4 2-) show competitive correlations. At elevated relative humidity (RH), no major spectral changes were observed in the XPS results, except for the growth of an oxygen component originating from condensed H2O. Near-edge X-ray absorption fine structure (NEXAFS) measurements show that the magnesium and sodium spectra are sensitive to the presence of water, and the results imply that the surface is fully solvated already at RH = 5%. The surface solvation is also fully reversible as the RH is reduced. No major differences are observed between sample types and sample locations, indicating that the salts originated from saline lakes commonly have solvated surfaces under the environmental conditions on Earth.

Amplification of light within aerosol particles accelerates in-particle photochemistry.

Optical confinement (OC) structures the optical field and amplifies light intensity inside atmospheric aerosol particles, with major consequences for sunlight-driven aerosol chemistry. Although theorized, the OC-induced spatial structuring has so far defied experimental observation. Here, x-ray spectromicroscopic imaging complemented by modeling provides direct evidence for OC-induced patterning inside photoactive particles. Single iron(III)-citrate particles were probed using the iron oxidation state as a photochemical marker. Based on these results, we predict an overall acceleration of photochemical reactions by a factor of two to three for most classes of atmospheric aerosol particles. Rotation of free aerosol particles and intraparticle molecular transport generally accelerate the photochemistry. Given the prevalence of OC effects, their influence on aerosol particle photochemistry should be considered by atmospheric models.

New-onset non-lesional aphasic status epilepticus. Clinical description, diagnostic clues, and treatment algorithm.

OBJECTIVES: De novo aphasic status epilepticus (ASE) in patients without a previous history of epilepsy and without cerebral lesions (aphasic NOSE) is rare. The aim of the study is to describe its clinical characteristics, etiologies, and outcome. MATERIALS & METHODS: Single-center study including consecutive patients presenting to the emergency department between 2011 and 2019 with acute aphasia, which was finally diagnosed as aphasic NOSE. Subsequent episodes of aphasia (>5 min) were recorded and divided into confirmed ASE and postictal aphasic episodes (non-ASE). Clinical characteristics of the two types of episodes were compared. RESULTS: Nineteen patients were included, suffering fifty episodes of epileptic aphasia, episodes per patient 2.6 (range 1-7). Fifteen patients (71.4%) were women, mean age at ASE onset was 66.05 years old (SD 6.3). Nine (47%) patients died, 6 of them (66.7%) during the aphasic episode. Ictal EEG was available in 37 episodes, confirming the diagnosis of ASE in 12 episodes; in 8 episodes, the EEG fulfilled the criteria of possible ASE. The most frequent etiologies were inflammatory and vascular. Comparing ASE with non-ASE episodes, ASE was longer than non-ASE (225 vs 65 h, p .024) and was treated more frequently with BZD (76 vs 24%, p .001) but with a longer delay (22.2 vs 1.5 h, p .06). CONCLUSIONS: ASE is a treatable, highly relapsing emergency, with the subsequent relapses ASE or postictal aphasia. EEG is diagnostic in half of the patients, while in others imaging techniques are also useful. Benzodiazepines should be administered. Persistent aphasia, of more than 65 hours' duration, is highly suggestive of ASE.

Impact of Tetrabutylammonium on the Oxidation of Bromide by Ozone.

The reaction of ozone with sea-salt derived bromide is relevant for marine boundary layer atmospheric chemistry. The oxidation of bromide by ozone is enhanced at aqueous interfaces. Ocean surface water and sea spray aerosol are enriched in organic compounds, which may also have a significant effect on this reaction at the interface. Here, we assess the surface propensity of cationic tetrabutylammonium at the aqueous liquid-vapor interface by liquid microjet X-ray photoelectron spectroscopy (XPS) and the effect of this surfactant on ozone uptake to aqueous bromide solutions. The results clearly indicate that the positively charged nitrogen group in tetrabutylammonium (TBA), along with its surface activity, leads to an enhanced interfacial concentration of both bromide and the bromide ozonide reaction intermediate. In parallel, off-line kinetic experiments for the same system demonstrate a strongly enhanced ozone loss rate in the presence of TBA, which is attributed to an enhanced surface reaction rate. We used liquid jet XPS to obtain detailed chemical composition information from the aqueous-solution-vapor interface of mixed aqueous solutions containing bromide or bromide and chloride with and without TBA surfactant. Core level spectra of Br 3d, C 1s, Cl 2p, N 1s, and O 1s were used for this comparison. A model was developed to account for the attenuation of photoelectrons by the carbon-rich layer established by the TBA surfactant. We observed that the interfacial density of bromide is increased by an order of magnitude in solutions with TBA. The salting-out of TBA in the presence of 0.55 M sodium chloride is apparent. The increased interfacial bromide density can be rationalized by the association constants for bromide and chloride to form ion-pairs with TBA. Still, the interfacial reactivity is not increasing simply proportionally with the increasing interfacial bromide concentration in response to the presence of TBA. The steady state concentration of the bromide ozonide intermediate increases by a smaller degree, and the lifetime of the intermediate is 1 order of magnitude longer in the presence of TBA. Thus, the influence of cationic surfactants on the reactivity of bromide depends on the details of the complex environment at the interface.

Risk of Developing Epilepsy after Autoimmune Encephalitis.

BACKGROUND: Acute symptomatic seizures (ASS) are a common manifestation of autoimmune encephalitis (AE), but the risk of developing epilepsy as a sequela of AE remains unknown, and factors predisposing the development of epilepsy have not been fully identified. OBJECTIVE: To assess the risk of developing epilepsy in AE and study related risk factors. MATERIALS AND METHODS: This was a retrospective single centre study including patients diagnosed with AE according to criteria described by Graus et al., with a minimum follow-up of 12 months after AE resolution. The sample was divided according to whether patients developed epilepsy or not. RESULTS: A total of 19 patients were included; 3 (15.8%) had AE with intracellular antibodies, 9 (47.4%) with extracellular antibodies, and 7 (36.8%) were seronegative. During follow-up, 3 patients (15.8%) died, 4 (21.1%) presented relapses of AE, and 11 (57.89%) developed epilepsy. There was a significant association between the development of epilepsy and the presence of hippocampal atrophy in control brain magnetic resonance imaging (MRI) (p = 0.037), interictal epileptiform discharges (IED) on control electroencephalogram (EEG) (p = 0.045), and immunotherapy delay (p = 0.016). CONCLUSIONS: Hippocampal atrophy in neuroimaging, IED on EEG during follow-up, and immunotherapy delay could be predictors of the development of epilepsy in patients with AE.

Photolytic radical persistence due to anoxia in viscous aerosol particles.

In viscous, organic-rich aerosol particles containing iron, sunlight may induce anoxic conditions that stabilize reactive oxygen species (ROS) and carbon-centered radicals (CCRs). In laboratory experiments, we show mass loss, iron oxidation and radical formation and release from photoactive organic particles containing iron. Our results reveal a range of temperature and relative humidity, including ambient conditions, that control ROS build up and CCR persistence in photochemically active, viscous organic particles. We find that radicals can attain high concentrations, altering aerosol chemistry and exacerbating health hazards of aerosol exposure. Our physicochemical kinetic model confirmed these results, implying that oxygen does not penetrate such particles due to the combined effects of fast reaction and slow diffusion near the particle surface, allowing photochemically-produced radicals to be effectively trapped in an anoxic organic matrix.

Quantitative profiling of built environment bacterial and fungal communities reveals dynamic material dependent growth patterns and microbial interactions.

Indoor microbial communities vary in composition and diversity depending on material type, moisture levels, and occupancy. In this study, we integrated bacterial cell counting, fungal biomass estimation, and fluorescence-assisted cell sorting (FACS) with amplicon sequencing of bacterial (16S rRNA) and fungal (ITS) communities to investigate the influence of wetting on medium density fiberboard (MDF) and gypsum wallboard. Surface samples were collected longitudinally from wetted materials maintained at high relative humidity (~95%). Bacterial and fungal growth patterns were strongly time-dependent and material-specific. Fungal growth phenotypes differed between materials: spores dominated MDF surfaces while fungi transitioned from spores to hyphae on gypsum. FACS confirmed that most of the bacterial cells were intact (viable) on both materials over the course of the study. Integrated cell count and biomass data (quantitative profiling) revealed that small changes in relative abundance often resulted from large changes in absolute abundance, while negative correlations in relative abundances were explained by rapid growth of only one group of bacteria or fungi. Comparisons of bacterial-bacterial and fungal-bacterial networks suggested a top-down control of fungi on bacterial growth, possibly via antibiotic production. In conclusion, quantitative profiling provides novel insights into microbial growth dynamics on building materials with potential implications for human health.

Seizures and epilepsy of autoimmune origin: A long-term prospective study.

OBJECTIVE: To follow prospectively a group of patients with seizures or epilepsy and suggestive clinical features of autoimmune aetiology and find out how many are finally diagnosed with acute symptomatic seizures (ASS) secondary to autoimmune encephalitis or autoimmune-related epilepsy, and how many develop epilepsy. METHODS: Consecutive patients meeting the inclusion criteria from 2010 to 2018 were identified. Patients were classified as confirmed, probable autoimmune, non-autoimmune, or unknown. RESULTS: One-hundred and nine patients were included, 64 (48.7 %) women, mean age 55.2 years (SD 17.9). ASS were reported by 61 patients (56 %), while 48 presented epilepsy (44 %). During follow-up 18 patients died (16.5 %). Final diagnosis was autoimmune-relatedepilepsy (confirmed + probable) in 22 cases and ASS secondary to autoimmune encephalitis (confirmed or probable) in 27, non-autoimmune aetiologies or other diagnosis in 49 (44 %), and unknown aetiology in 11 (10.2 %). Neuronal antibodies (ab) were found in 27 patients (24.7 %). T-lymphocyte infiltration in temporal lobes was observed in 2/8 patients (20 %). Neuronal ab were more frequent in the autoimmune groups: 17 patients (29.8 %) vs 1(2.3 %), p:0.001, and they suffered more autoimmune diseases: 37 (75.5 %) vs 12 (24.48 %), p:0.0001, and 34 (69 %) vs 22 (44.9 %) p:0.027, respectively. All patients with GAD ab 17/17 (100 %) evolved to chronic disease. Four patients (29 %) with ASS secondary to autoimmune encephalitis developed epilepsy. SIGNIFICANCE: ASS secondary to autoimmune encephalitis or autoimmune-related epilepsy will be diagnosed in nearly half of patients who have been suspected of it. The only diagnostic clue is neuronal ab. Patients who have suffered ASS secondary to autoimmune encephalitis may develop epilepsy over time.

Commensal Oral Rothia mucilaginosa Produces Enterobactin, a Metal-Chelating Siderophore.

Next-generation sequencing studies of saliva and dental plaque from subjects in both healthy and diseased states have identified bacteria belonging to the Rothia genus as ubiquitous members of the oral microbiota. To gain a deeper understanding of molecular mechanisms underlying the chemical ecology of this unexplored group, we applied a genome mining approach that targets functionally important biosynthetic gene clusters (BGCs). All 45 genomes that were mined, representing Rothia mucilaginosa, Rothia dentocariosa, and Rothia aeria, harbored a catechol-siderophore-like BGC. To explore siderophore production further, we grew the previously characterized R. mucilaginosa ATCC 25296 in liquid cultures, amended with glycerol, which led to the identification of the archetype siderophore enterobactin by using tandem liquid chromatography-mass spectrometry (LC-MS/MS), high-performance liquid chromatography (HPLC), and nuclear magnetic resonance (NMR) spectroscopy. Normally attributed to pathogenic gut bacteria, R. mucilaginosa is the first commensal oral bacterium found to produce enterobactin. Cocultivation studies including R. mucilaginosa or purified enterobactin revealed that enterobactin reduced growth of certain strains of cariogenic Streptococcus mutans and pathogenic strains of Staphylococcus aureus Commensal oral bacteria were either unaffected, reduced in growth, or induced to grow adjacent to enterobactin-producing R. mucilaginosa or the pure compound. Taken together with Rothia's known capacity to ferment a variety of carbohydrates and amino acids, our findings of enterobactin production add an additional level of explanation to R. mucilaginosa's prevalence in the oral cavity. Enterobactin is the strongest Fe(III) binding siderophore known, and its role in oral health requires further investigation.IMPORTANCE The communication language of the human oral microbiota is vastly underexplored. However, a few studies have shown that specialized small molecules encoded by BGCs have critical roles such as in colonization resistance against pathogens and quorum sensing. Here, by using a genome mining approach in combination with compound screening of growth cultures, we identified that the commensal oral community member R. mucilaginosa harbors a catecholate-siderophore BGC, which is responsible for the biosynthesis of enterobactin. The iron-scavenging role of enterobactin is known to have positive effects on the host's iron pool and negative effects on host immune function; however, its role in oral health remains unexplored. R. mucilaginosa was previously identified as an abundant community member in cystic fibrosis, where bacterial iron cycling plays a major role in virulence development. With respect to iron's broad biological importance, iron-chelating enterobactin may explain R. mucilaginosa's colonization success in both health and disease.

Aging induced changes in ice nucleation activity of combustion aerosol as determined by near edge X-ray absorption fine structure (NEXAFS) spectroscopy.

Fresh soot particles are generally hydrophobic, however, particle hydrophilicity can be increased through atmospheric aging processes. At present little is known on how particle chemical composition and hydrophilicity change upon atmospheric aging and associated uncertainties governing the ice cloud formation potential of soot. Here we sampled two propane flame soots referred to as brown and black soot, characterized as organic carbon rich and poor, respectively. We investigated how the ice nucleation activity of these particles changed through aging in water and aqueous acidic solutions, using a continuous flow diffusion chamber operated at cirrus cloud temperatures (T ≤ 233 K). Single aggregates of both unaged and aged soot were chemically characterized by scanning transmission X-ray microscopy and near edge X-ray absorption fine structure (STXM/NEXAFS) measurements. Particle wettability was determined through water sorption measurements. Unaged black and brown soot particles exhibited significantly different ice nucleation activities. Our experiments revealed significantly enhanced ice nucleation activity of the aged soot particles compared to the fresh samples, lowering the required relative humidities at which ice formation can take place at T = 218 K by up to 15% with respect to water (ΔRHi ≈ 25%). We observed an enhanced water uptake capacity for the aged compared to the unaged samples, which was more pronounced for the black soot. From these measurements we concluded that there is a change in ice nucleation mechanism when aging brown soot. Comparison of the NEXAFS spectra of unaged soot samples revealed a unique spectral feature around 287.5 eV in the case of black soot that was absent for the brown soot, indicative of carbon with hydroxyl functionalities. Comparison of the NEXAFS spectra of unaged and aged soot particles indicates changes in organic functional groups, and the aged spectra were found to be largely similar across soot types, with the exception of the water aged brown soot. Overall, we conclude that atmospheric aging is important to representatively assess the ice cloud formation activity of soot particles.

The premature closure of ROMPA clinical trial: mortality reduction in septic shock by plasma adsorption.

OBJECTIVES: Coupled Plasma Filtration and Adsorption (CPFA) use in septic shock remains controversial. The objective is to clarify whether the application of high doses of CPFA in addition to the current clinical practice could reduce hospital mortality in septic shock patients in Intensive Care Units at 28 days and at 90 days follow-up. DESIGN: We designed a prospective randomised clinical trial, Reducción de la Mortalidad Plasma-Adsorción (ROMPA), to demonstrate an absolute mortality reduction of 20% (α=0.05; 1-ß=0.8; n=190 (95×2)). SETTING: Being aware of the pitfalls associated with previous medical device trials, we developed a training programme to improve CPFA use (especially clotting problems). The protocol was approved by the ethics committees of all participating centres. Circumstances beyond our control produced a change in recruitment conditions unacceptable to ROMPA researchers and the trial was discontinued. PARTICIPANTS: By closure, five centres from an initial 10 fulfilled the necessary trial criteria, with 49 patients included, 30 in the control group (CG) and 19 in the intervention group (IG). INTERVENTION: CPFA. MAIN OUTCOME MEASURES: Hospital mortality at 28 days and 90 days follow-up. RESULTS: After 28 days, 14 patients died (46.7%) from the CG and 11 (57.9%) from the IG, not reaching statistical significance (p=0.444). At 90 days, 19 patients had died (63.3%) from the CG and 11 patients (57.9%) from the IG, (p=0.878). The adjustment by propensity score or the use of the Kaplan-Meier technique failed to achieve statistical difference, neither by Intention to Treat nor by the Actual Intervention Received. CONCLUSION: We herewith present the results gained from the prematurely closed trial. The results are inconclusive due to low statistical power but we consider that this data is of interest for the scientific community and potentially necessary for any ensuing debate. REGISTER: NCT02357433 in clinicaltrials.gov.

Letrozole treatment of pubertal female mice results in activational effects on reproduction, metabolism and the gut microbiome.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in reproductive-aged women that is comprised of two out of the following three features: hyperandrogenism, oligo- or amenorrhea, or polycystic ovaries. In addition to infertility, many women with PCOS have metabolic dysregulation that increases the risk of developing type 2 diabetes, hypertension, and non-alcoholic fatty liver disease. Changes in the gut microbiome are associated with PCOS and gut microbes may be involved in the pathology of this disorder. Since PCOS often manifests in the early reproductive years, puberty is considered to be a critical time period for the development of PCOS. Exposure to sex steroid hormones during development results in permanent, organizational effects, while activational effects are transient and require the continued presence of the hormone. Androgens exert organizational effects during prenatal or early post-natal development, but it is unclear whether androgen excess results in organizational or activational effects during puberty. We recently developed a letrozole-induced PCOS mouse model that recapitulates both reproductive and metabolic phenotypes of PCOS. In this study, we investigated whether letrozole treatment of pubertal female mice exerts organizational or activational effects on host physiology and the gut microbiome. Two months after letrozole removal, we observed recovery of reproductive and metabolic parameters, as well as diversity and composition of the gut microbiome, indicating that letrozole treatment of female mice during puberty resulted in predominantly activational effects. These results suggest that if exposure to excess androgens during puberty leads to the development of PCOS, reduction of androgen levels during this time may improve reproductive and metabolic phenotypes in women with PCOS. These results also imply that continuous letrozole exposure is required to model PCOS in pubertal female mice since letrozole exerts activational rather than organizational effects during puberty.