Search

Inventories for global aerosol and aerosol precursor emissions have been collected (based on published inventories and published simulations), assessed and prepared for the year 2000 (present-day conditions) and for the year 1750 (pre-industrial conditions). These global datasets establish a comprehensive source for emission input to global modeling, when simulating the aerosol impact on climate with state-of-the-art aerosol component modules. As these modules stratify aerosol into dust, sea-salt, sulfate, organic matter and soot, for all these aerosol types global fields on emission strength and recommendations for injection altitude and particulate size are provided. Temporal resolution varies between daily (dust and sea-salt), monthly (wild-land fires) and annual (all other emissions). These datasets benchmark aerosol emissions according to the knowledge in the year 2004. They are intended to serve as systematic constraints in sensitivity studies of the AeroCom initiative, which seeks to quantify (actual) uncertainties in aerosol global modeling.

This paper suggests a method for improving current inventories of aerosol emissions from biomass burning. The method is based on the hypothesis that, although the total estimates within large regions are correct, the exact spatial and temporal description can be improved. It makes use of open fire detection from the ATSR instrument that is available since 1996. The emissions inventories are re-distributed in space and time according to the occurrence of open fires. Although the method is based on the night-time hot-spot product of the ATSR, other satellite biomass burning proxies (AVHRR, TRMM, GLOBSCAR and GBA2000) show similar distributions. The impact of the method on the emission inventories is assessed using an aerosol transport model, the results of which are compared to sunphotometer and satellite data. The seasonal cycle of aerosol load in the atmosphere is significantly improved in several regions, in particular South America and Australia. Besides, the use of ATSR fire detection may be used to account for interannual events, as is demonstrated on the large Indonesian fires of 1997, a consequence of the 1997-1998 El Niño. Despite these improvements, there are still some large discrepancies between the simulated and observed aerosol optical thicknesses resulting from biomass burning emissions.

The aim of this study was to investigate the effects of lithium on brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and glial cell line-derived neurotrophic factor (GDNF) expression in the hippocampus and on memory in experimental pneumococcal meningitis. The mood-stabilizer lithium is known as a neuroprotective agent with many effects on the brain. In this study, animals received either artificial cerebrospinal fluid or Streptococcus pneumoniae suspension at a concentration of 5 × 109 CFU/mL. Eighteen hours after induction, all animals received ceftriaxone. The animals received saline or lithium (47.5 mg/kg) or tamoxifen (1 mg/kg) as adjuvant treatment, and they were separated into six groups: control/saline, control/lithium, control/tamoxifen, meningitis/saline, meningitis/lithium, and meningitis/tamoxifen. Ten days after meningitis induction, animals were subjected to open-field habituation and the step-down inhibitory avoidance tasks. Immediately after these tasks, the animals were killed and their hippocampus was removed to evaluate the expression of BDNF, NGF, and GDNF. In the meningitis group, treatment with lithium and tamoxifen resulted in improvement in memory. Meningitis group showed decreased expression of BDNF and GDNF in the hippocampus while lithium reestablished the neurotrophin expression. Lithium was able to prevent memory impairment and reestablishes hippocampal neurotrophin expression in experimental pneumococcal meningitis.

Abstract Background Sepsis is a potentially fatal disease characterized by acute organ failure that affects more than 30 million people worldwide. Inflammation is strongly associated with sepsis, and patients can experience impairments in memory, concentration, verbal fluency, and executive functioning after being discharged from the hospital. We hypothesize that sepsis disrupts the microbiota–gut–brain axis homeostasis triggering cognitive impairment. This immune activation persists during treatment, causing neurological dysfunction in sepsis survivors. Methods To test our hypothesis, adult Wistar rats were subjected to cecal–ligation and perforation (CLP) or sham (non-CLP) surgeries. The animals were subjected to the [11C]PBR28 positron emission tomography (PET)/computed tomography (CT) imaging at 24 h and 10 days after CLP and non-CLP surgeries. At 24 h and 10 days after surgery, we evaluated the gut microbiome, bacterial metabolites, cytokines, microglia, and astrocyte markers. Ten days after sepsis induction, the animals were subjected to the novel object recognition (NOR) and the Morris water maze (MWM) test to assess their learning and memory. Results Compared to the control group, the 24-h and 10-day CLP groups showed increased [11C]PBR28 uptake, glial cells count, and cytokine levels in the brain. Results show that sepsis modulates the gut villus length and crypt depth, alpha and beta microbial diversities, and fecal short-chain fatty acids (SCFAs). In addition, sepsis surviving animals showed a significant cognitive decline compared with the control group. Conclusions Since several pharmacological studies have failed to prevent cognitive impairment in sepsis survivors, a better understanding of the function of glial cells and gut microbiota can provide new avenues for treating sepsis patients.

Abstract A biomarker describes a measurable indicator of a patient's clinical condition that can be measured accurately and reproducibly. Biomarkers offer utility for diagnosis, prognosis, early disease recognition, risk stratification, appropriate treatment (theranostics), and trial enrichment for patients with sepsis or suspected sepsis. In this narrative review, we aim to answer the question, "Do biomarkers in patients with sepsis or septic shock predict mortality, multiple organ dysfunction syndrome (MODS), or organ dysfunction?" We also discuss the role of pro- and anti-inflammatory biomarkers and biomarkers associated with intestinal permeability, endothelial injury, organ dysfunction, blood–brain barrier (BBB) breakdown, brain injury, and short and long-term mortality. For sepsis, a range of biomarkers is identified, including fluid phase pattern recognition molecules (PRMs), complement system, cytokines, chemokines, damage-associated molecular patterns (DAMPs), non-coding RNAs, miRNAs, cell membrane receptors, cell proteins, metabolites, and soluble receptors. We also provide an overview of immune response biomarkers that can help identify or differentiate between systemic inflammatory response syndrome (SIRS), sepsis, septic shock, and sepsis-associated encephalopathy. However, significant work is needed to identify the optimal combinations of biomarkers that can augment diagnosis, treatment, and good patient outcomes.

ABSTRACT Pneumococcal meningitis, inflammation of the meninges due to an infection of the Central Nervous System caused by Streptococcus pneumoniae (the pneumococcus), is the most common form of community-acquired bacterial meningitis globally. Aquaporin 4 (AQP4) water channels on astrocytic end feet regulate the solute transport of the glymphatic system, facilitating the exchange of compounds between the brain parenchyma and the cerebrospinal fluid (CSF), which is important for the clearance of waste away from the brain. Wistar rats, subjected to either pneumococcal meningitis or artificial CSF (sham control), received Evans blue-albumin (EBA) intracisternally. Overall, the meningitis group presented a significant impairment of the glymphatic system by retaining the EBA in the CSF compartments compared to the uninfected sham group. Our results clearly showed that during pneumococcal meningitis, the glymphatic system does not function because of a detachment of the astrocytic end feet from the blood-brain barrier (BBB) vascular endothelium, which leads to misplacement of AQP4 with the consequent loss of the AQP4 water channel's functionality. IMPORTANCE The lack of solute drainage due to a dysfunctional glymphatic system leads to an increase of the neurotoxic bacterial material in the CSF compartments of the brain, ultimately leading to brain-wide neuroinflammation and neuronal damage with consequent impairment of neurological functions. The loss of function of the glymphatic system can therefore be a leading cause of the neurological sequelae developing post-bacterial meningitis.

The microbiota-gut-brain axis is a bidirectional signaling mechanism between the gastrointestinal tract and the central nervous system. The complexity of the intestinal ecosystem is extraordinary; it comprises more than 100 trillion microbial cells that inhabit the small and large intestine, and this interaction between microbiota and intestinal epithelium can cause physiological changes in the brain and influence mood and behavior. Currently, there has been an emphasis on how such interactions affect mental health. Evidence indicates that intestinal microbiota are involved in neurological and psychiatric disorders. This review covers evidence for the influence of gut microbiota on the brain and behavior in Alzheimer disease, dementia, anxiety, autism spectrum disorder, bipolar disorder, major depressive disorder, Parkinson’s disease, and schizophrenia. The primary focus is on the pathways involved in intestinal metabolites of microbial origin, including short-chain fatty acids, tryptophan metabolites, and bacterial components that can activate the host’s immune system. We also list clinical evidence regarding prebiotics, probiotics, and fecal microbiota transplantation as adjuvant therapies for neuropsychiatric disorders.

Abstract Background Bacterial meningitis is a devastating central nervous system (CNS) infection with acute and long-term neurological consequences, including cognitive impairment. The aim of this study was to understand the association between activated microglia-induced neuroinflammation and post-meningitis cognitive impairment. Method Meningitis was induced in male Wistar rats by injecting Streptococcus pneumoniae into the brain through the cisterna magna, and rats were then treated with ceftriaxone. Twenty-four hours and 10 days after meningitis induction, rats were imaged with positron emission tomography (PET) using [11C]PBR28, a specific translocator protein (TSPO) radiotracer, to determine in vivo microglial activation. Following imaging, the expression of TSPO, cardiolipin, and cytochrome c, inflammatory mediators, oxidative stress markers, and glial activation markers were evaluated in the prefrontal cortex and hippocampus. Ten days after meningitis induction, animals were subjected to behavioral tests, such as the open-field, step-down inhibitory avoidance, and novel object recognition tests. Results Both 24-h (acute) and 10-day (long-term) groups of rats demonstrated increased [11C]PBR28 uptake and microglial activation in the whole brain compared to levels in the control group. Although free from infection, 10-day group rats exhibited increased expression levels of cytokines and markers of oxidative stress, microglial activation (IBA-1), and astrocyte activation (GFAP) similar to those seen in the 24-h group. Acute meningitis induction also elevated TSPO, cytochrome c, and caspase-3 levels with no change in caspase-9 levels. Furthermore, upregulated levels of TSPO, cytochrome c, and caspase-3 and caspase-9 were observed in the rat hippocampus 10 days after meningitis induction with a simultaneous reduction in cardiolipin levels. Animals showed a cognitive decline in all tasks compared with the control group, and this impairment may be at least partially mediated by activating a glia-mediated immune response and upregulating TSPO. Conclusions TSPO-PET could potentially be used as an imaging biomarker for microglial activation and long-term cognitive impairment post-meningitis. Additionally, this study opens a new avenue for the potential use of TSPO ligands after infection-induced neurological sequelae.

Objective: To evaluate the influence of environmental enrichment (EE) on memory, cytokines, and brain-derived neurotrophic factor (BDNF) in the brain of adult rats subjected to experimental pneumococcal meningitis during infancy. Methods: On postnatal day 11, the animals received either artificial cerebrospinal fluid (CSF) or Streptococcus pneumoniae suspension intracisternally at 1 × 106 CFU/mL and remained with their mothers until age 21 days. Animals were divided into the following groups: control, control + EE, meningitis, and meningitis + EE. EE began at 21 days and continued until 60 days of age (adulthood). EE consisted of a large cage with three floors, ramps, running wheels, and objects of different shapes and textures. At 60 days, animals were randomized and subjected to habituation to the open-field task and the step-down inhibitory avoidance task. After the tasks, the hippocampus and CSF were isolated for analysis. Results: The meningitis group showed no difference in performance between training and test sessions of the open-field task, suggesting habituation memory impairment; in the meningitis + EE group, performance was significantly different, showing preservation of habituation memory. In the step-down inhibitory avoidance task, there were no differences in behavior between training and test sessions in the meningitis group, showing aversive memory impairment; conversely, differences were observed in the meningitis + EE group, demonstrating aversive memory preservation. In the two meningitis groups, IL-4, IL-10, and BDNF levels were increased in the hippocampus, and BDNF levels in the CSF. Conclusions: The data presented suggest that EE, a non-invasive therapy, enables recovery from memory deficits caused by neonatal meningitis.

Invasion of the central nervous system (CNS) by microorganisms is a severe and frequently fatal event during the course of many infectious diseases. It may lead to deafness, blindness, cerebral palsy, hydrocephalus, cognitive impairment or permanent neurological dysfunction in survivors. Pathogens can cross the blood-brain barrier by transcellular migration, paracellular migration and in infected macrophages. Pathogens may breach the blood-brain barrier and be recognized by antigen-presenting cells through the binding of Toll-like receptors. This induces the activation of nuclear factor kappa B or mitogen-activated protein kinase pathways and subsequently induces leukocyte infiltration and proliferation and the expression of numerous proteins involved in inflammation and the immune response. Many brain cells can produce cytokines, chemokines and other pro-inflammatory molecules in response to bacteria stimuli; as a consequence, polymorphonuclear cells are attracted and activated, and release large amounts of superoxide anion and nitric oxide, leading to peroxynitrite formation and oxidative stress. This cascade leads to lipid peroxidation, mitochondrial damage and blood-brain barrier breakdown, contributing to cellular injury during neuronal infection. Current evidence suggests that bacterial CNS infections can play a role in the etiopathogenesis of behavioral disorders by increasing pro-inflammatory cytokines and bacterial virulence factors. The aim of this review is to summarize the current knowledge of the relevant pathophysiologic steps in CNS infections.

Pneumococcal meningitis is a life-threatening disease characterized by an acute purulent infection affecting piamater, arachnoid and the subarachnoid space. The intense inflammatory host's response is potentially fatal and contributes to the neurological sequelae. Streptococcus pneumoniae colonizes the nasopharynx, followed by bacteremia, microbial invasion and blood-brain barrier traversal. S. pneumoniae is recognized by antigen-presenting cells through the binding of Toll-like receptors inducing the activation of factor nuclear kappa B or mitogen-activated protein kinase pathways and subsequent up-regulation of lymphocyte populations and expression of numerous proteins involved in inflammation and immune response. Many brain cells can produce cytokines, chemokines and others pro-inflammatory molecules in response to bacteria stimuli, as consequence, polymorphonuclear are attracted, activated and released in large amounts of superoxide anion and nitric oxide, leading to the peroxynitrite formation, generating oxidative stress. This cascade leads to lipid peroxidation, mitochondrial damage, blood-brain barrier breakdown contributing to cell injury during pneumococcal meningitis.

Introduction: Mortality and morbidity from bacterial meningitis in African adults is significantly higher than those in better resourced settings. At the same time, the periodontal diseases are highly prevalent and can affect up to 90% of the population. Dental caries in Uganda was recorded in 40% and 62.5% of the children and adults, respectively. We hypothesize that pneumococcal meningitis could interfere in the development of periapical lesion. The aim of this study was to evaluate periapical lesion in Wistar rats subjected to pneumococcal meningitis. Materials and Methods: The animals were divided in control, control/periapical lesion, meningitis, and meningitis/periapical lesion groups. The surgical exposure of molars and the infection of the dental pulp were from the oral environment. Pulp necrosis was induced on the left mandibular first molars during adulthood. Dental pulps were exposed by drilling cavities on the central portion of the occlusal surface with a 1011 HL round bur in high speed to a depth nearly equal to the bur diameter. Animals were subjected to behavioral task and evaluation of the size of periodontal ligament. Data from periodontal ligament space and open field task were reported as mean ± SEM and analysed by Two-way ANOVA and paired Student’s t-test, respectively. Results and Conclusion: Meningitis/periapical increased the periodontal ligament space by 61% when compared with control/ periapical. In the open-field task, there were no differences in the number of crossings and rearing movements between training and test session in meningitis and periapical lesion groups demonstrating habituation memory impairment. Bacterial meningitis and periapical lesion may play an important role in development of cognitive impairment.

Severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) causes the coronavirus disease 2019 (COVID-19), which has been declared a public health emergency of international interest, with confirmed cases in most countries. COVID-19 presents manifestations that can range from asymptomatic or mild infections up to severe manifestations that lead to hospitalization and death. A growing amount of evidence indicates that the virus may cause neuroinvasion. Postmortem brain study findings have included edema, hemorrhage, hydrocephalus, atrophy, encephalitis, infarcts, swollen axons, myelin loss, gliosis, neuronal satellitosis, hypoxic-ischemic damage, arteriolosclerosis, leptomeningeal inflammation, neuronal loss, and axon degeneration. In addition, the COVID-19 pandemic is causing dangerous effects on the mental health of the world population, some of which can be attributed to its social impact (social distancing, financial issues, and quarantine). There is also a concern that environmental stressors, enhanced by psychological factors, are contributing to the emergence of psychiatric outcomes during the pandemic. Although clinical studies and diagnosing SARS-CoV-2-related neurological disease can be challenging, they are necessary to help define the manifestations and burden of COVID-19 in neurological and psychiatric symptoms during and after the pandemic. This review aims to present the neurobiology of coronavirus and postmortem neuropathological hallmarks.

In September 2017, numerous measurement stations recorded large surface concentrations of Ru106 in Europe. This event was well recorded by various monitoring stations worldwide and offer a valuable framework to compare the modelling strategies deployed to quickly evaluate where the plume goes and with what concentrations. In general, the source and its intensity are not known and hypotheses have to be done. Models have to be fast and accurate: Lagrangian and Eulerian are often used but rarely compared. In this study, the FLEXPART Lagrangian model and the WRF-CHIMERE Eulerian models are used to simulate the emissions, transport and deposition of this source of Ru106. First, it is shown that the hypothesis of location, timing and intensity of the source is realistic, by comparison to surface measurements. Second, sensitivity analysis performed with the Eulerian model and several transport scheme showed that this model may provide better results than the Lagrangian one. It opens the door to further development, including chemistry and mixing with other pollutants during these specific events., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The French National Data Center (NDC) uses an automated simulation of the 133 Xe worldwide atmospheric background as one of the means to categorize the radionuclide measurements of the Comprehensive Nuclear-Test-Ban Treaty (CTBT) International Monitoring System (IMS). These simulations take into account 133 Xe releases from the known or assumed major industrial emitters in the world and global-scale meteorological data. However, a quantification of the simulation uncertainties in this operational set up is yet to be addressed. This work discusses the benefits of meteorological ensemble data as available from National Centers for Environmental Prediction (NCEP) for that purpose. For this study, the daily dispersion of releases from the Institute for Radio Elements (IRE), a medical isotope production facility located in Fleurus (Belgium), was calculated over one year with emissions measured in-site and ensemble meteorological data. The ensemble contains 31 members, which resulted in as many predictions of activity concentration for any given time and place. The resulting distribution statistics (mean, median and spread), and the control run, were confronted to the deterministic run and to measurements at one IMS-like station near Paris (France) and one IMS station in Freiburg (Germany). Overall, the ensemble results have decreased the simulation performance, as expected given the use of meteorological analyses only. However, contrasting patterns were found with a detailed analysis of daily activity concentration over two one-month-and-a-half periods. Noticeably, outlier results were found to carry the best forecast in some significant detections, proving their relevance for the measurement categorization, despite their isolated character. Importantly, the ensemble has allowed the quantification of meteorological uncertainties, which was beneficial in all cases. It either has improved the confidence of IMS data categorization or has pointed to low confidence predictions. A criterion to identify the latter is suggested, based on information provided by the ensemble distributions. In addition, maps of probability of detections and of relative spread are suggested to show additional benefits of ensemble meteorology., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

A global-scale simulation of the 133 Xe atmospheric background is automated at the French National Data Center (NDC) for the purpose of categorizing the radionuclide measurements of the Comprehensive Nuclear-Test-Ban Treaty (CTBT) International Monitoring System (IMS). These simulations take into account 133 Xe releases from all known major industrial emitters in the world, compiled from the literature and described as constant values. Emission data measured directly at the stack of the Institute for Radio Elements (IRE), a medical isotope production facility located in Fleurus (Belgium), were implemented in the simulations with a time resolution of 15 minutes. This work discusses the contribution of real (measured) emissions to the prediction of the 133 Xe atmospheric background at IMS noble gas stations and at a location near Paris, for which IMS-like 133 Xe measurements were available. For the purpose of this study, simulations initiated with the IRE measured emissions were run in parallel to those with the a priori emissions used to date. The benefits of including actual emissions in the simulations were found as a function of the distance between the station and the source of the release. At the closest stations, i.e., near Paris (France) and at Schauinsland, Freiburg (Germany), respectively 250 and 400 km from Fleurus, the simulated activity concentrations differed by a factor greater than 2 more than one third of the time, and by a factor of more than 5 about 10% of the time. No significant or detectable differences were found beyond 1500-2000 km. Furthermore, at the Paris station, the timing of the measured peaks was better reproduced with the actual emission data. However, not all peak amplitudes were correctly reproduced even though the real emissions were used, highlighting the remaining uncertainties, primarily in the meteorological data and transport modeling., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Somatic cell reprogramming is the process that allows differentiated cells to revert to a pluripotent state. In contrast to the extensively studied rewiring of epigenetic and transcriptional programs required for reprogramming, the dynamics of post-transcriptional changes and their associated regulatory mechanisms remain poorly understood. Here we study the dynamics of alternative splicing changes occurring during efficient reprogramming of mouse B cells into induced pluripotent stem (iPS) cells and compare them to those occurring during reprogramming of mouse embryonic fibroblasts., Results: We observe a significant overlap between alternative splicing changes detected in the two reprogramming systems, which are generally uncoupled from changes in transcriptional levels. Correlation between gene expression of potential regulators and specific clusters of alternative splicing changes enables the identification and subsequent validation of CPSF3 and hnRNP UL1 as facilitators, and TIA1 as repressor of mouse embryonic fibroblasts reprogramming. We further find that these RNA-binding proteins control partially overlapping programs of splicing regulation, involving genes relevant for developmental and morphogenetic processes., Conclusions: Our results reveal common programs of splicing regulation during reprogramming of different cell types and identify three novel regulators of this process and their targets.

Atmospheric transport modeling has been used to interpret the unprecedented number of multi-isotope detections of radioxenons observed during the six months of the qualification process by the Comprehensive Nuclear-Test-Ban Treaty Organization of the new SPALAX-NG system (Système de Prélèvement Automatique en Ligne avec l'Analyse du Xénon - Nouvelle Génération). Highest 133 Xe activity concentrations were found to be systematically associated with the concomitant measurement of several other radioxenons at the prevailing wind direction of north/northeast pointing to the Institute for Radio Elements (IRE), a medical isotope production facility located in Fleurus (Belgium). The lowest 133 Xe activity concentrations were not associated with a prevailing wind direction or other radioxenons, indicating the contribution of distant sources (global background). The IRE's average source terms for 133m Xe and to a lesser extent for 133 Xe (slightly overestimated by a factor of 1.7) showed good agreement with the literature values, while corrections by a factor of ~23 and ~53 were proposed for 131m Xe and 135 Xe since the initial values were underestimated. However, detections of 131m Xe alone and some low-activity concentrations of 133 Xe associated with only one of the other radioxenons could not be linked to the IRE releases. Analysis of these cases suggests the contribution of local source releases that have been difficult to identify to date. In addition to the global background, releases from such local sources, if not identified, could affect the analysis of the isotopic ratios measured following a nuclear test. The characterization of these local contributions is now possible owing to the capacity of the SPALAX-NG and other new generation measurements systems., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The SPALAX-NG is a new-generation system that is designed to detect radioactive xenon at trace levels in the atmosphere following a nuclear explosion or civilian source release. This new system formed part of a validation program led by the Provisional Technical Secretary of the Comprehensive Nuclear-Test-Ban Treaty (CTBT) Organization. In this study, the first SPALAX-NG unit was tested for six months between October 2018 and April 2019 at the CEA/DIF premises near Paris, France. This test period provided an outstanding opportunity to illustrate the high level of detectability and reliability of the system. The data availability obtained over this period was approximately 99%, which was well above the CTBT Data Availability criteria of 95%. The data reliability was demonstrated by a comparison with a collocated SPALAX-1 unit (former version of SPALAX) and by re-measuring several samples at the CTBT-certified French laboratory FRL08. The high sensitivity to the detection of the four relevant radioxenon isotopes was fully demonstrated and enabled the recording of a major dataset for western Europe. A large set of isotopic ratios was measured, which enabled the discrimination criteria between civilian sources and nuclear test signatures to be refined., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The relationship between inflammatory bowel disease (IBD) and mood disorders is complex and involves overlapping metabolic pathways, which may determine comorbidity. Several studies have been shown that this comorbidity could worsen IBD clinical course. The treatment of ulcerative colitis is complex, and involves traditional therapy to promote the function of epithelial barrier, reducing exacerbated inflammatory responses. Recently, it has been shown that some probiotic strains could modulate gut-brain axis, reducing depressive and anxiety scores in humans, including IBD patients. Accordingly, this study aimed to evaluate the role of Weissella paramesenteroides WpK4 in murine models of ulcerative colitis and chronic stress. It was observed that bacterium ingestion improved health of colitis mice, reducing intestinal permeability, besides improving colon histopathological appearance. In stressed mice, bacterial consumption was associated with a reduced anxiety-like and depressive-like behaviors. In both assays, the beneficial role of W. paramesenteroides WpK4 was related to its immunomodulatory feature. It is possible to state that W. paramesenteroides WpK4 exerted their beneficial roles in gut-brain axis through their immunomodulatory effects with consequences in several metabolic pathways related to intestinal permeability and hippocampal physiology., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

After performing a first multi-model exercise in 2015 a comprehensive and technically more demanding atmospheric transport modelling challenge was organized in 2016. Release data were provided by the Australian Nuclear Science and Technology Organization radiopharmaceutical facility in Sydney (Australia) for a one month period. Measured samples for the same time frame were gathered from six International Monitoring System stations in the Southern Hemisphere with distances to the source ranging between 680 (Melbourne) and about 17,000 km (Tristan da Cunha). Participants were prompted to work with unit emissions in pre-defined emission intervals (daily, half-daily, 3-hourly and hourly emission segment lengths) and in order to perform a blind test actual emission values were not provided to them. Despite the quite different settings of the two atmospheric transport modelling challenges there is common evidence that for long-range atmospheric transport using temporally highly resolved emissions and highly space-resolved meteorological input fields has no significant advantage compared to using lower resolved ones. As well an uncertainty of up to 20% in the daily stack emission data turns out to be acceptable for the purpose of a study like this. Model performance at individual stations is quite diverse depending largely on successfully capturing boundary layer processes. No single model-meteorology combination performs best for all stations. Moreover, the stations statistics do not depend on the distance between the source and the individual stations. Finally, it became more evident how future exercises need to be designed. Set-up parameters like the meteorological driver or the output grid resolution should be pre-scribed in order to enhance diversity as well as comparability among model runs., (Copyright © 2018. Published by Elsevier Ltd.)

The International Monitoring System (IMS) is part of the verification regime for the Comprehensive Nuclear-Test-Ban-Treaty Organization (CTBTO). At entry-into-force, half of the 80 radionuclide stations will be able to measure concentrations of several radioactive xenon isotopes produced in nuclear explosions, and then the full network may be populated with xenon monitoring afterward. An understanding of natural and man-made radionuclide backgrounds can be used in accordance with the provisions of the treaty (such as event screening criteria in Annex 2 to the Protocol of the Treaty) for the effective implementation of the verification regime. Fission-based production of (99)Mo for medical purposes also generates nuisance radioxenon isotopes that are usually vented to the atmosphere. One of the ways to account for the effect emissions from medical isotope production has on radionuclide samples from the IMS is to use stack monitoring data, if they are available, and atmospheric transport modeling. Recently, individuals from seven nations participated in a challenge exercise that used atmospheric transport modeling to predict the time-history of (133)Xe concentration measurements at the IMS radionuclide station in Germany using stack monitoring data from a medical isotope production facility in Belgium. Participants received only stack monitoring data and used the atmospheric transport model and meteorological data of their choice. Some of the models predicted the highest measured concentrations quite well. A model comparison rank and ensemble analysis suggests that combining multiple models may provide more accurate predicted concentrations than any single model. None of the submissions based only on the stack monitoring data predicted the small measured concentrations very well. Modeling of sources by other nuclear facilities with smaller releases than medical isotope production facilities may be important in understanding how to discriminate those releases from releases from a nuclear explosion., (Published by Elsevier Ltd.)

The newly synthesized mutant L501fsX533 Frizzled-4 form and the alpha3beta4 nicotinic acetylcholine receptor expressed in the absence of nicotine accumulate in the endoplasmic reticulum of COS-7 cells and induce the formation of large areas of smooth and highly convoluted cisternae. This results in a generalized block of the transport to the Golgi complex of newly synthesized proteins. Intriguingly, both effects happen peculiarly in COS-7 cells; HeLa, Huh-7, and HEK293 cells expressing the two receptors at similar level than COS-7 cells show normal ER and normal transport toward the plasma membrane. These results question the conclusion that a dominant-negative mechanism would explain the dominance of the mutant L501fsX533 Fz4 allele in the transmission of a form of Familial exudative vitreoretinopathy. Moreover, they indicate that the coordination of endoplasmic reticulum homeostasis in COS-7 cells is particularly error prone. This finding suggests that COS-7 cells may be extremely useful to study the molecular mechanisms regulating endoplasmic reticulum size and architecture.

Pneumococcal meningitis is associated with neurologic sequelae, such as learning and memory impairment. Most recently, a nonbacteriolytic antibiotic has been investigated to minimise the inflammatory host response and prevent cognitive damage. In this study, we compared daptomycin (DPTO) or ceftriaxone (CFX) treatment on the inflammatory parameters and on the blood-brain barrier (BBB) integrity in experimental pneumococcal meningitis. In the first experiment, the animals received 10 µl of a Streptococcus pneumoniae suspension or artificial cerebrospinal fluid by intracerebroventricular (i.c.v.) and were treated with CFX or DPTO at 18 h post-infection. The animals were euthanised at 18, 20, 24, 36 and 40 h post-infection. In the hippocampus, brain-derived neurotrophic factor (BDNF), tumour necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and IL-10 levels were not different between treatment groups; however, IL-4 and cytokine-induced neutrophil chemoattractant 1 (CINC-1) levels decreased in the CFX group. In the frontal cortex, TNF-α, IL- 4, IL-6, IL-10 and BDNF levels were not different between treatment groups. Only CINC-1 levels decreased at 40 h postinfection with CFX treatment. In the second experiment, the animals received DPTO or CFX for 7 days and were euthanised 10 days after pneumococcal meningitis induction. TNF-α, IL-6, IL-10, CINC-1 and BDNF levels were not different between treatment groups in the hippocampus; however, IL-4 levels decreased in CFX group. In the third experiment, the animals received 10 µl of an S. pneumoniae suspension or artificial CSF by i.c.v. and were treated with a single dose of CFX or DTPO antibiotic; assessment of the BBB breakdown showed that both antibiotics prevented the BBB disruption. Both treatments equally protected the BBB integrity, and there were no significant difference in cytokine production.

Aims and Objectives: To estimate the diagnostic value and determine the feasibility of the NEECHAM Confusion Scale on critically ill older patients., Background: Delirium is a common syndrome in hospitalised older patients, especially in surgical intensive care units, and the consequences of under-detection can be very serious for older people. Therefore, assessment of the cognitive status of older patients using a valid instrument is important in intensive care units., Design: A descriptive prospective design was used., Methods: Consecutive nonintubated patients aged 65 and older, admitted to a surgical intensive care unit of an Italian hospital during a seven months period, were assessed for delirium using the NEECHAM scale and the Confusion Assessment Method for intensive care unit, once per shift, for 48 hours after admission. Cohen's kappa coefficient, ROC curve, sensitivity and specificity were estimated. An open ended questionnaire was used to assess user-friendliness of the scale., Results: A sample of 41 older patients with a mean age of 78·3 years was studied. The kappa coefficient was 0·95. The sensitivity was 99·19%, specificity 95% at cut-off of 25, and the area under the curve was 0·99 (CI 0·99-1·00). Nurses evaluated positively the scale as they were able to collect data during care process in maximum 10 minutes, but experienced problems in rating the appearance behaviour and physiological control items of the scale., Conclusions: Findings from this study confirm the good diagnostic value and ease of application of the NEECHAM scale with nonventilated intensive care patients., Relevance to Clinical Practice: The NEECHAM scale can be used to detect delirium during the routine nursing assessment of nonintubated older patients as it requires minimal demand and stress on the patient as well as on the bedside nurse., (© 2012 Blackwell Publishing Ltd.)

Aerosol concentration and cloud droplet radii derived from space-borne measurements are used to explore the effect of aerosols on cloud microphysics. Cloud droplet size is found to be largest (14 micrometers) over remote tropical oceans and smallest (6 micrometers) over highly polluted continental areas. Small droplets are also present in clouds downwind of continents. By using estimates of droplet radii coupled with aerosol load, a statistical mean relationship is derived. The cloud droplet size appears to be better correlated with an aerosol index that is representative of the aerosol column number under some assumptions than with the aerosol optical thickness. This study reveals that the effect of aerosols on cloud microphysics is significant and occurs on a global scale.