Perivascular spaces, plasma GFAP, and speeded executive function in neurodegenerative diseases.

INTRODUCTION: We investigated the effect of perivascular spaces (PVS) volume on speeded executive function (sEF), as mediated by white matter hyperintensities (WMH) volume and plasma glial fibrillary acidic protein (GFAP) in neurodegenerative diseases. METHODS: A mediation analysis was performed to assess the relationship between neuroimaging markers and plasma biomarkers on sEF in 333 participants clinically diagnosed with Alzheimer's disease/mild cognitive impairment, frontotemporal dementia, or cerebrovascular disease from the Ontario Neurodegenerative Disease Research Initiative. RESULTS: PVS was significantly associated with sEF (c = -0.125 ± 0.054, 95% bootstrap confidence interval [CI] [-0.2309, -0.0189], p = 0.021). This effect was mediated by both GFAP and WMH. DISCUSSION: In this unique clinical cohort of neurodegenerative diseases, we demonstrated that the effect of PVS on sEF was mediated by the presence of elevated plasma GFAP and white matter disease. These findings highlight the potential utility of imaging and plasma biomarkers in the current landscape of therapeutics targeting dementia. HIGHLIGHTS: Perivascular spaces (PVS) and white matter hyperintensities (WMH) are imaging markers of small vessel disease. Plasma glial fibrillary protein acidic protein (GFAP) is a biomarker of astroglial injury. PVS, WMH, and GFAP are relevant in executive dysfunction from neurodegeneration. PVS's effect on executive function was mediated by GFAP and white matter disease.

Evaluation and utilisation of privacy enhancing technologies-A data spaces perspective.

Data sharing has facilitated the digitisation of society. We can access our bank accounts or make an appointment with our doctor anytime and anywhere. To achieve this, we have to share certain information, whether personal, professional, etc. This may seem like a minor cost for an individual user, but actually the data economy as the backbone of a digital transformation that is reshaping all aspects of human life. However, one of the major concerns arises regarding what happens to such individual data; once shared, control over it is often lost. For that reason, users and companies are reluctant to share their data. The European Union, through its European Strategy for Data, is establishing a policy and legal framework for establishing a single market for data in Europe by improving the trust and fairness of the data economy. Data spaces are a commitment to sharing data in a reliable and secure way, but this endeavour should, of course, not be at the expense of privacy rights. In recent years, Privacy-Enhancing Technologies (PETs) have emerged to achieve data sharing and privacy preservation that can address the requirements of data spaces around sensitive citizen and business data. In this work, we review existing PETs and assess their relevance, technological maturity, and applicability in the context of common European data spaces. Finally, we illustrate the benefits of secure data sharing via Federated Learning in a healthcare use case, where the preservation of privacy is a primer requirement and is therefore to be guaranteed.

On the Inclusion Relations of Global Ultradifferentiable Classes Defined by Weight Matrices.

We study and characterize the inclusion relations of global classes in the general weight matrix framework in terms of growth relations for the defining weight matrices. We consider the Roumieu and Beurling cases, and as a particular case, we also treat the classical weight function and weight sequence cases. Moreover, we construct a weight sequence which is oscillating around any weight sequence which satisfies some minimal conditions and, in particular, around the critical weight sequence ( p ! ) 1 / 2 , related with the non-triviality of the classes. Finally, we also obtain comparison results both on classes defined by weight functions that can be defined by weight sequences and conversely.

Smart Partitioned Blockchain.

Blockchain is a developing technology that promises advancements when it is applied to other fields. Applying blockchain to other systems requires a customized blockchain model to satisfy the requirements of different application fields. One important area is to integrate blockchain with smart spaces and the Internet of Things to process, manage, and store data. Actually, smart spaces and Internet of Things systems include various types of transactions in terms of sensitivity. The sensitivity can be considered as correctness sensitivity, time sensitivity, and specialization sensitivity. Correctness sensitivity means that the systems should accept precise or approximated data in some cases, whereas time sensitivity means that there are time bounds for each type of transaction, and specialization sensitivity applies when some transactions are processed only by specialized people. Therefore, this work introduces the smart partitioned blockchain model, where we use machine learning and deep learning models to classify transactions into different pools according to their sensitivity levels. Then, each pool is mapped to a specific part of the smart partitioned blockchain model. The parts can be permissioned or permissionless. The permissioned parts can have different sub-parts if needed. Consequently, the smart partitioned blockchain can be customized to meet application-field requirements. In the experimental results, we use bank and medical datasets with a predefined sensitivity threshold for classification accuracy in each system. The bank transactions are critical, whereas the classification of the medical dataset is speculative and less critical. The Random Forest model is used for bank-dataset classification, and its accuracy reaches 100%, whereas Sequential Deep Learning is used for the medical dataset, which reaches 91%. This means that all bank transactions are correctly mapped to the corresponding parts of the blockchain, whereas accuracy is lower for the medical dataset. However, acceptability is determined based on the predefined sensitivity threshold.

Ant3D-A Fisheye Multi-Camera System to Survey Narrow Spaces.

Although the field of geomatics has seen multiple technological advances in recent years which enabled new applications and simplified the consolidated ones, some tasks remain challenging, inefficient, and time- and cost-consuming. This is the case of accurate tridimensional surveys of narrow spaces. Static laser scanning is an accurate and reliable approach but impractical for extensive tunnel environments; on the other hand, portable laser scanning is time-effective and efficient but not very reliable without ground control constraints. This paper describes the development process of a novel image-based multi-camera system meant to solve this specific problem: delivering accurate, reliable, and efficient results. The development is illustrated from the system conceptualization and initial investigations to the design choices and requirements for accuracy. The resulting working prototype has been put to the test to verify the effectiveness of the proposed approach.

Safe Zones for Facial Fillers: Anatomical Study of SubSMAS Spaces in Asians.

The study "Spaces of the Face for Filler Procedures: Identification of subSMAS Spaces Based on Anatomical Study" explores the anatomy of facial spaces crucial for safe and effective filler injections. By delineating the subSMAS (sub-superficial musculoaponeurotic system) spaces, this research highlights how these virtual compartments, bordered by fat, muscles, fascia, and ligaments, facilitate independent muscle movement and reduce the risk of damaging critical structures. The thicker and more robust skin of East Asians necessitates deeper filler injections, emphasizing the significance of accurately identifying these spaces. A cadaver study with dyed gelatin validated the existence and characteristics of these subSMAS spaces, confirming their safety for filler procedures. Key spaces, such as the subgalea-frontalis, interfascial and temporalis, and prezygomatic spaces, were examined, illustrating safe zones for injections. The findings underscore the importance of anatomical knowledge for enhancing facial aesthetics while minimizing complications. This study serves as a guide for clinicians to perform precise and safe filler injections, providing a foundation for further research on the dynamic interactions of these spaces and long-term outcomes.

Hydrophobia, dis/connection, and difference: Understanding Chinese immigrants' fear of coastal swimming in Aotearoa New Zealand.

New Zealand's coastal blue spaces, from harbours to beaches, provide diverse wellbeing benefits but can also be sites of danger, fear, and cultural contestation. This qualitative research focuses on Chinese migrants in Auckland, a community who are underrepresented in coastal recreation and overrepresented in drowning statistics. Findings show Chinese migrants dis/connection with coastal blue space and fear of coastal swimming, derived from their homeland habitus and lack of coastal 'blue space' cultural capital. Our research contributes to the growing recognition of 'hydrophobia', and how the racialisation of leisure space impacts the potential for blue spaces and practices to be therapeutic.

Effects of simulated multi-sensory stimulation integration on physiological and psychological restoration in virtual urban green space environment.

Virtual urban green environment images and audio stimuli had been proven to have restorative effects on subjects' physical and mental health. In this area, researchers predominantly focused on visual, auditory and olfactory aspects, while tactile and gustatory senses have been minimally explored. However, the optimal combination of sensory stimuli for promoting physical and mental recovery remains unclear. Therefore, a simulated sensory stimulation approach involving 240 participants was employed, with 30 individuals included in each of the eight experimental groups: the visual-auditory (VA), visual-auditory-olfactory (VAO), visual-auditory-tactile (VAT), visual-auditory-gustatory(VAG), visual-auditory-olfactory-tactile (VAOT), visual-auditory-olfactory-gustatory (VAOG), visual-auditory-tactile-gustatory (VATG), and visual-auditory-olfactory-tactile-gustatory (VAOTG) groups. This study aimed to explore the differences in participants' physiological and psychological health recovery after exposure to different combinations of simulated sensory stimuli in virtual UGSs. The results indicated that the following: (1) In terms of physiological recovery, the blood pressure of the 8 experimental groups decreased significantly after the experiment, indicating that the virtual urban green space environment has a certain recovery effect on physiological state. The combination of VAOTG stimuli in the multisensory group resulted in the best blood pressure recovery (p < 0.05). Tactile is an important sense to enhance the physiological recovery effect. Olfactory-tactile or tactile-gustatory stimuli interactions significantly enhance physiological recovery, emphasizing the importance of tactile stimulation in improving physiological recovery. (2) In terms of psychological recovery, the common trigger of olfactory-gustatory is the most key element to enhance psychological recovery through multi-sensory stimulation of virtual urban green space environment. VAOG stimulation had the best effect on psychological recovery (p < 0.05), followed by VAOTG stimulation (p < 0.05). Gustatory is an important sense to enhance the psychological recovery effect, and both the tactile-gustatory interaction and the olfactory-gustatory interaction significantly enhance the recovery effect. At the same time, the psychological recovery effect obtained by four or more sensory combinations was higher than that obtained by two or three sensory stimulation groups. This study confirms more possibilities for ways to restore physical and mental health through virtual natural environments. It expands the research on the benefits of virtual nature experience and provides theoretical support for the application of this method.

Regulation of brain fluid volumes and pressures: basic principles, intracranial hypertension, ventriculomegaly and hydrocephalus.

The principles of cerebrospinal fluid (CSF) production, circulation and outflow and regulation of fluid volumes and pressures in the normal brain are summarised. Abnormalities in these aspects in intracranial hypertension, ventriculomegaly and hydrocephalus are discussed. The brain parenchyma has a cellular framework with interstitial fluid (ISF) in the intervening spaces. Framework stress and interstitial fluid pressure (ISFP) combined provide the total stress which, after allowing for gravity, normally equals intracerebral pressure (ICP) with gradients of total stress too small to measure. Fluid pressure may differ from ICP in the parenchyma and collapsed subarachnoid spaces when the parenchyma presses against the meninges. Fluid pressure gradients determine fluid movements. In adults, restricting CSF outflow from subarachnoid spaces produces intracranial hypertension which, when CSF volumes change very little, is called idiopathic intracranial hypertension (iIH). Raised ICP in iIH is accompanied by increased venous sinus pressure, though which is cause and which effect is unclear. In infants with growing skulls, restriction in outflow leads to increased head and CSF volumes. In adults, ventriculomegaly can arise due to cerebral atrophy or, in hydrocephalus, to obstructions to intracranial CSF flow. In non-communicating hydrocephalus, flow through or out of the ventricles is somehow obstructed, whereas in communicating hydrocephalus, the obstruction is somewhere between the cisterna magna and cranial sites of outflow. When normal outflow routes are obstructed, continued CSF production in the ventricles may be partially balanced by outflow through the parenchyma via an oedematous periventricular layer and perivascular spaces. In adults, secondary hydrocephalus with raised ICP results from obvious obstructions to flow. By contrast, with the more subtly obstructed flow seen in normal pressure hydrocephalus (NPH), fluid pressure must be reduced elsewhere, e.g. in some subarachnoid spaces. In idiopathic NPH, where ventriculomegaly is accompanied by gait disturbance, dementia and/or urinary incontinence, the functional deficits can sometimes be reversed by shunting or third ventriculostomy. Parenchymal shrinkage is irreversible in late stage hydrocephalus with cellular framework loss but may not occur in early stages, whether by exclusion of fluid or otherwise. Further studies that are needed to explain the development of hydrocephalus are outlined.

Assessing the conservation value of cemeteries to urban biota worldwide.

Cemeteries are key urban green spaces with multifaceted societal and ecological importance. Their biodiversity is shaped by unique environmental and cultural factors. They can potentially protect rare and endangered species, yet their conservation value compared with other urban green spaces remains largely unexplored. We sought to fill this gap by systematically reviewing literature to investigate the conservation value of cemeteries relative to other urban green spaces (botanical gardens, institutional premises, natural remnants, and parks) by comparing species richness and proportions of native and unique species. We analyzed data from 70 papers covering 50 cities in 27 countries with linear and binomial mixed-effects models at both site and city level. Cemetery conservation value was similar to urban parks, except for the proportion of unique species, for which parks had significantly higher proportions (21.9% vs. 14.2%, p < 0.001). Cemeteries hosted slightly higher proportions of native species at the city level than botanical gardens (99.7% vs. 99.6%, p < 0.001) and institutional green spaces (96.3% vs. 94.1%, p = 0.034) and proportions comparable to parks and natural remnants (p > 0.05). They also had similar or higher values than institutional premises in species richness and unique species proportions (p > 0.05) and a higher site-level proportion of native species (p < 0.001). In contrast, species richness (slopes = -0.11 and -0.25, respectively) and unique species proportions (4.4% and 6.9%, respectively, p < 0.001 for both) were lower in cemeteries than in remnants of natural areas and in botanical gardens. The conservation value of cemeteries and parks was similar for animals, but parks had a higher value for plants. Overall, cemeteries were generally at least as valuable as some other green spaces for urban biodiversity and mostly native biota. Their religious and cultural significance suggests they will remain intact in the long term; thus, it is essential to prioritize and further promote their biodiversity in conservation and sustainable urban design plans.

Análisis del valor de conservación que tienen los cementerios para la biota urbana a nivel mundial Resumen Los cementerios son espacios urbanos verdes con una importancia social y ecológica multifacética. Su biodiversidad está moldeada por factores ambientales y culturales únicos. Los cementerios tienen el potencial para proteger especies raras y en peligro, pero su valor de conservación sigue sin ser explorado cuando se compara con otros espacios urbanos verdes. Buscamos llenar este vacío con una revisión sistemática de la bibliografía para investigar el valor de conservación de los cementerios en relación a otros espacios urbanos verdes (jardines botánicos, sedes institucionales, remanentes naturales y parques) al comparar la riqueza de especies y la proporción de especies nativas y únicas. Analizamos con modelos lineales y binomiales de efectos mixtos a nivel de sitio y de ciudad los datos de 70 artículos enfocados en 50 ciudades de 27 países. El valor de conservación de los cementerios fue similar al de los parques urbanos, excepto para la proporción de especies únicas, para la cual los parques tuvieron una proporción significativamente más alta (21.9% vs. 14.2%, p<0.001). A nivel de ciudad, los cementerios albergaron una proporción ligeramente mayor de especies nativas en comparación con los jardines botánicos (99.7% vs. 99.6%, p<0.001) y las sedes institucionales (96.3% vs. 94.1%, p = 0.034) y tuvieron una proporción comparable a los parques y los remanentes naturales (p>0.05). Los cementerios también tuvieron un valor similar o mayor a los espacios verdes institucionales en cuanto a riqueza de especies y proporción de especies únicas (p>0.05) y una proporción mayor a nivel de sitio de especies nativas (p<0.001). Al contrario, la riqueza de especies (pendientes = ­0.11 y ­0.25, respectivamente) y la proporción de especies únicas (4.4% y 6.9%, respectivamente, p<0.001 para ambas) fueron menores en los cementerios que en los remanentes de las áreas naturales y en los jardines botánicos. El valor de conservación de los cementerios y los parques fue similar para los animales, pero los parques tuvieron un valor mayor para las plantas. En general, los cementerios fueron al menos tan valiosos como otros espacios verdes para la biodiversidad urbana y casi toda la biota nativa. El significado religioso y cultural que tienen los cementerios sugiere que seguirán intactos a largo plazo; por ello, es esencial priorizar y promover aún más su biodiversidad en la conservación y en los planes de diseño urbano sustentable.

Urban heatwave, green spaces, and mental health: A review based on environmental health risk assessment framework.

Utilizing the framework of environmental health risk assessment and healing, the article reviews the effectiveness and potential of green space systems in mitigating the impact of high temperatures, promoting mental health, and improving the risk characteristics of high-temperature heat waves. We utilized CiteSpace software to conduct a time-zone analysis of the relationship between heatwaves, green spaces, and health using clustered data from 2001 to 2023. This study evaluates the role of green space systems in mitigating high temperatures and enhancing mental health within the environmental health risk assessment framework. Using CiteSpace software, we analyzed literature from 2001 to 2023, focusing on the interactions among heatwaves, green spaces, and health. Our results indicate that most existing research concentrates on hazard identification, with insufficient exploration of the dose-response relationships between green spaces and temperature reduction. Quantitative studies on green space design and spatial optimization are scarce, and guidance on effective configurations remains limited. Additionally, the health impacts of heatwaves vary by region, with a noticeable imbalance in research focus; Asia and Africa, in particular, are underrepresented in studies addressing heatwave effects. We conclude that effective mitigation strategies require: (1) a comprehensive environmental health risk assessment framework that integrates advanced methods like big data analysis and geospatial simulations to improve green space planning and design; (2) further theoretical exploration into the mechanisms by which green spaces regulate temperature and mental health, including detailed analysis of spatiotemporal patterns and the functional optimization of green space structures; and (3) the development of robust parameterized design guidance based on specific therapeutic dosages (green space stimulus) to optimize configurations and enhance the effectiveness of green spaces in mitigating adverse mental health impacts from deteriorating thermal environments. Future research should prioritize underrepresented regions, focusing on exposure levels, dose-response relationships, and high-temperature warning systems while fostering multidisciplinary collaboration to develop effective urban planning and climate adaptation strategies.

Efficient context-aware computing: a systematic model for dynamic working memory updates in context-aware computing.

The expanding computer landscape leads us toward ubiquitous computing, in which smart gadgets seamlessly provide intelligent services anytime, anywhere. Smartphones and other smart devices with multiple sensors are at the vanguard of this paradigm, enabling context-aware computing. Similar setups are also known as smart spaces. Context-aware systems, primarily deployed on mobile and other resource-constrained wearable devices, use a variety of implementation approaches. Rule-based reasoning, noted for its simplicity, is based on a collection of assertions in working memory and a set of rules that regulate decision-making. However, controlling working memory capacity efficiently is a key challenge, particularly in the context of resource-constrained systems. The paper's main focus lies in addressing the dynamic working memory challenge in memory-constrained devices by introducing a systematic method for content removal. The initiative intends to improve the creation of intelligent systems for resource-constrained devices, optimize memory utilization, and enhance context-aware computing.

On Orlicz classes defined in terms of associated weight functions.

N-functions and their growth and regularity properties are crucial in order to introduce and study Orlicz classes and Orlicz spaces. We consider N-functions which are given in terms of so-called associated weight functions. These functions are frequently appearing in the theory of ultradifferentiable function classes and in this setting additional information is available since associated weight functions are defined in terms of a given weight sequence. We express and characterize several known properties for N-functions purely in terms of weight sequences which allows to construct (counter-) examples. Moreover, we study how for abstractly given N-functions this framework becomes meaningful and finally we establish a connection between the complementary N-function and the recently introduced notion of the so-called dual sequence.

Non-hemorrhagic imaging markers of cerebral amyloid angiopathy in memory clinic patients.

INTRODUCTION: The Boston criteria v2.0 for cerebral amyloid angiopathy (CAA) incorporated non-hemorrhagic imaging markers. Their prevalence and significance in patients with cognitive impairment remain uncertain. METHODS: We studied 622 memory clinic patients with available magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) biomarkers. Two raters assessed non-hemorrhagic markers, and we explored their association with clinical characteristics through multivariate analyses. RESULTS: Most patients had mild cognitive impairment; median age was 71 years and 50% were female. Using the v2.0 criteria, possible or probable CAA increased from 75 to 383 patients. Sixty-eight percent of the sample had non-hemorrhagic CAA markers, which were independently associated with age (odds ratio [OR] = 1.04, 95% confidence interval [CI] = 1.01-1.07), female sex (OR = 1.68, 95% CI = 1.11-2.54), and hemorrhagic CAA markers (OR = 2.11, 95% CI = 1.02-4.35). DISCUSSION: Two-thirds of patients from a memory clinic cohort had non-hemorrhagic CAA markers, increasing the number of patients meeting the v2.0 CAA criteria. Longitudinal approaches should explore the implications of these markers, particularly the hemorrhagic risk in this population. HIGHLIGHTS: The updated Boston criteria for cerebral amyloid angiopathy (CAA) now include non-hemorrhagic markers. The prevalence of non-hemorrhagic CAA markers in memory clinic patients is unknown. Two-thirds of patients in our memory clinic presented non-hemorrhagic CAA markers. The presence of these markers was associated with age, female sex, and hemorrhagic CAA markers. The hemorrhagic risk of patients presenting these type of markers remains unclear.

The Ocular Glymphatic System-Current Understanding and Future Perspectives.

The ocular glymphatic system subserves the bidirectional polarized fluid transport in the optic nerve, whereby cerebrospinal fluid from the brain is directed along periarterial spaces towards the eye, and fluid from the retina is directed along perivenous spaces following upon its axonal transport across the glial lamina. Fluid homeostasis and waste removal are vital for retinal function, making the ocular glymphatic fluid pathway a potential route for targeted manipulation to combat blinding ocular diseases such as age-related macular degeneration, diabetic retinopathy, and glaucoma. Several lines of work investigating the bidirectional ocular glymphatic transport with varying methodologies have developed diverging mechanistic models, which has created some confusion about how ocular glymphatic transport should be defined. In this review, we provide a comprehensive summary of the current understanding of the ocular glymphatic system, aiming to address misconceptions and foster a cohesive understanding of the topic.

Systematic review and meta-analysis of automated methods for quantifying enlarged perivascular spaces in the brain.

Research into magnetic resonance imaging (MRI)-visible perivascular spaces (PVS) has recently increased, as results from studies in different diseases and populations are cementing their association with sleep, disease phenotypes, and overall health indicators. With the establishment of worldwide consortia and the availability of large databases, computational methods that allow to automatically process all this wealth of information are becoming increasingly relevant. Several computational approaches have been proposed to assess PVS from MRI, and efforts have been made to summarise and appraise the most widely applied ones. We systematically reviewed and meta-analysed all publications available up to September 2023 describing the development, improvement, or application of computational PVS quantification methods from MRI. We analysed 67 approaches and 60 applications of their implementation, from 112 publications. The two most widely applied were the use of a morphological filter to enhance PVS-like structures, with Frangi being the choice preferred by most, and the use of a U-Net configuration with or without residual connections. Older adults or population studies comprising adults from 18 years old onwards were, overall, more frequent than studies using clinical samples. PVS were mainly assessed from T2-weighted MRI acquired in 1.5T and/or 3T scanners, although combinations using it with T1-weighted and FLAIR images were also abundant. Common associations researched included age, sex, hypertension, diabetes, white matter hyperintensities, sleep and cognition, with occupation-related, ethnicity, and genetic/hereditable traits being also explored. Despite promising improvements to overcome barriers such as noise and differentiation from other confounds, a need for joined efforts for a wider testing and increasing availability of the most promising methods is now paramount.

Clinical Importance of Grading Tumor Spread through Air Spaces in Early-Stage Small-Lung Adenocarcinoma.

This study aimed to identify the clinical manifestation and implications according to the grading of tumor spread through air spaces in early-stage small (≤2 cm) pathological stage I non-mucinous lung adenocarcinomas. Medical records of patients with pathological stage I tumors sized ≤2 cm were retrospectively reviewed and analyzed. The furthest distance of the spread through air spaces from the tumor margin was measured on a standard-length scale (mm). Enrolled patients were categorized into spread through air spaces (STAS) (-) and STAS (+), and STAS (+) was subdivided according to its furthest distance as follows: STAS (+)-L (<2 mm) and STAS (+)-H (≥2 mm). Risk factors for STAS (+) included papillary predominant subtype (p = 0.027), presence of micropapillary patterns (p < 0.001), and EGFR (p = 0.039). The overall survival of the three groups did not differ significantly (p = 0.565). The recurrence-free survival of STAS (+)-H groups was significantly lower than those of STAS (-) and STAS (+)-L (p < 0.001 and p = 0.039, respectively). A number of alveolar spaces were definite risk factors for STAS (+)-H groups (p < 0.001), and male gender could be one (p = 0.054). In the patient group with small (≤2 cm) pathological stage I lung adenocarcinomas, the presence of STAS ≥ 2 mm was related to significantly lower recurrence-free survival. For identifying definite risk factors for the presence of farther STAS, more precise analysis from a larger study population should be undertaken.

A physiological model for iohexol plasma clearance supporting diagnostics of kidney function.

BACKGROUND: There are several shortcomings in present methods for estimation of GFR from plasma clearance. The aim of the present study was therefore to develop a physiologically based method for calculation of plasma clearance of iohexol. METHODS: A mechanistic model founded on classical biochemical engineering principles where in- and outgoing molecular flows of iohexol between plasma and surrounding tissues were balanced over time. After intravenous injections of iohexol, plasma samples were taken from the investigated subjects until complete elimination of iohexol. After tuning of the model parameters, the clearance value was calculated from the injected dose and the integral of the iohexol concentrations over the investigated period. RESULTS: The mass balance model was able to predict the time course of iohexol distribution and elimination after parameterization of mass balance and kinetic equations. Four model structures were evaluated, all based on model parameters derived from published data and from internal tests, each complied at varying physiological conditions. Iohexol clearance was assessed through the model and compared with calculations from previously practiced methods. When testing the mass balance model on ten healthy subjects, clearance was estimated accurately. CONCLUSIONS: The physiological and mechanistic character of the mass balance model may suggest that its derived clearance comes closer to actual in vivo conditions than data derived from previously practiced calculation methods. Although here, only verified with the clearance marker iohexol, the mass balance model should be applicable also to other renal clearance markers.

The influence of pre- and postnatal exposure to air pollution and green spaces on infant's gut microbiota: Results from the MAMI birth cohort study.

BACKGROUND: Animal and human studies indicate that exposure to air pollution and natural environments might modulate the gut microbiota, but epidemiological evidence is very scarce. OBJECTIVES: To assess the potential impact of pre- and postnatal exposure to air pollution and green spaces on infant gut microbiota assembly and trajectories during the first year of life. METHODS: MAMI ("MAternal MIcrobes") birth cohort (Valencia, Spain, N = 162) was used to study the impact of environmental exposure (acute and chronic) on infant gut microbiota during the first year of life (amplicon-based 16S rRNA sequencing). At 7 days and at 1, 6 and 12 months, residential pre- and postnatal exposure to air pollutants (NO2, black carbon -BC-, PM2.5 and O3) and green spaces indicators (NDVI and area of green spaces at 300, 500 and 1000 m buffers) were obtained. For the association between exposures and alpha diversity indicators linear regression models (cross-sectional analyses) and mixed models, including individual as a random effect (longitudinal analyses), were applied. For the differential taxon analysis, the ANCOM-BC package with a log count transformation and multiple-testing corrections were used. RESULTS: Acute exposure in the first week of life and chronic postnatal exposure to NO2 were associated with a reduction in microbial alpha diversity, while the effects of green space exposure were not evident. Acute and chronic (prenatal or postnatal) exposure to NO2 resulted in increased abundance of Haemophilus, Akkermansia, Alistipes, Eggerthella, and Tyzerella populations, while increasing green space exposure associated with increased Negativicoccus, Senegalimassilia and Anaerococcus and decreased Tyzzerella and Lachnoclostridium populations. DISCUSSION: We observed a decrease in the diversity of the gut microbiota and signs of alteration in its composition among infants exposed to higher levels of NO2. Increasing green space exposure was also associated with changes in gut microbial composition. Further research is needed to confirm these findings.

Alterations in brain fluid physiology during the early stages of development of ischaemic oedema.

Oedema occurs when higher than normal amounts of solutes and water accumulate in tissues. In brain parenchymal tissue, vasogenic oedema arises from changes in blood-brain barrier permeability, e.g. in peritumoral oedema. Cytotoxic oedema arises from excess accumulation of solutes within cells, e.g. ischaemic oedema following stroke. This type of oedema is initiated when blood flow in the affected core region falls sufficiently to deprive brain cells of the ATP needed to maintain ion gradients. As a consequence, there is: depolarization of neurons; neural uptake of Na+ and Cl- and loss of K+; neuronal swelling; astrocytic uptake of Na+, K+ and anions; swelling of astrocytes; and reduction in ISF volume by fluid uptake into neurons and astrocytes. There is increased parenchymal solute content due to metabolic osmolyte production and solute influx from CSF and blood. The greatly increased [K+]isf triggers spreading depolarizations into the surrounding penumbra increasing metabolic load leading to increased size of the ischaemic core. Water enters the parenchyma primarily from blood, some passing into astrocyte endfeet via AQP4. In the medium term, e.g. after three hours, NaCl permeability and swelling rate increase with partial opening of tight junctions between blood-brain barrier endothelial cells and opening of SUR1-TPRM4 channels. Swelling is then driven by a Donnan-like effect. Longer term, there is gross failure of the blood-brain barrier. Oedema resolution is slower than its formation. Fluids without colloid, e.g. infused mock CSF, can be reabsorbed across the blood-brain barrier by a Starling-like mechanism whereas infused serum with its colloids must be removed by even slower extravascular means. Large scale oedema can increase intracranial pressure (ICP) sufficiently to cause fatal brain herniation. The potentially lethal increase in ICP can be avoided by craniectomy or by aspiration of the osmotically active infarcted region. However, the only satisfactory treatment resulting in retention of function is restoration of blood flow, providing this can be achieved relatively quickly. One important objective of current research is to find treatments that increase the time during which reperfusion is successful. Questions still to be resolved are discussed.