HDLs extract lipophilic drugs from cells.

High-density lipoproteins (HDLs) prevent cell death induced by a variety of cytotoxic drugs. The underlying mechanisms are however still poorly understood. Here, we present evidence that HDLs efficiently protect cells against thapsigargin (TG), a sarco/endoplasmic reticulum (ER) Ca2+-ATPase (SERCA) inhibitor, by extracting the drug from cells. Drug efflux could also be triggered to some extent by low-density lipoproteins and serum. HDLs did not reverse the non-lethal mild ER stress response induced by low TG concentrations or by SERCA knockdown, but HDLs inhibited the toxic SERCA-independent effects mediated by high TG concentrations. HDLs could extract other lipophilic compounds, but not hydrophilic substances. This work shows that HDLs utilize their capacity of loading themselves with lipophilic compounds, akin to their ability to extract cellular cholesterol, to reduce the cell content of hydrophobic drugs. This can be beneficial if lipophilic xenobiotics are toxic but may be detrimental to the therapeutic benefit of lipophilic drugs such as glibenclamide.

Anti-SSA Ro52 and anti-Ro60 autoantibodies: association with clinical phenotypes.

OBJECTIVES: Anti-SSA autoantibodies can be differentiated according to their antigenic target proteins as anti-Ro60 (60 kDa) or anti-Ro52 (52 kDa). Anti-SSA(Ro60) antibodies are clearly associated with connective tissue diseases (CTD), but the clinical significance of anti-SSA(Ro52) antibodies remains unclear. The aim of the present study was to analyse the disease phenotype of patients with anti-Ro52 and/or anti-Ro60 antibodies. METHODS: A multicentre, cross-sectional study was carried out of positive anti-Ro52 and/or Ro60 antibodies patients followed at 10 Rheumatology centres from January 2018 until December 2021. Patients were categorised into 3 groups: group 1 (Ro52+/Ro60-); group 2 (Ro52-/Ro60+); group 3 (Ro52+/Ro60+). Antinuclear antibodies were evaluated by indirect immunofluorescence assay and further screened for anti-extractable nuclear antigen (ENA) antibodies. Demographicsand clinical data were compared between the 3 groups, by patients' medical chart review. Univariate analysis was performed and subsequently logistic regression was used to identify intergroup differences and calculate the odds ratio with a 95% confidence interval (95% CI). RESULTS: We included 776 patients [female: 83.1%; median age: 59 (46-71) years]. Groups 1, 2, and 3 comprised 31.1%, 32.6%, and 36.3% of the patients, respectively. Anti-Ro52 antibody alone was more frequently associated with non-rheumatic diseases, older age, and men (p<0.05). Among patients with CTD, the diagnosis of systemic lupus erythematosus is 3 and 2 times more prevalent in groups 2 and 3, respectively, than in group 1 [OR 2.8 (95% CI 1.60, 4.97), p<0.001; OR 2.2 (95% CI 1.28, 3.86), p<0.01]. In group 2, the diagnosis of undifferentiated CTD is more frequent than in the other groups. Group 1 was more frequently associated with inflammatory myositis than group 2 [OR 0.09 (95% CI 0.01, 0.33), p<0.001] or group 3 [OR 0.08 (95% CI 0.01, 0.29), p<0.001]. Group 1 was also more frequently associated with arthritis (p<0.01), interstitial lung disease (p<0.01), and myositis (p<0.01). CONCLUSIONS: Anti-Ro52+ antibody alone is frequently found in patients with non-rheumatic diseases. In addition, anti-Ro52+ antibody is also prevalent in patients with CTD and associated with clinical phenotypes that are different from anti-Ro60+ antibody.

The role of nature reserves in conservation effectiveness of ecosystem services in China.

Establishing nature reserves (NRs) is a common method to avoid biodiversity loss and degradation of ecosystem services (ESs). The evaluation of ESs in NRs and the exploration of associated influencing factors are the basis for improving ESs and management. However, the ES effectiveness of NRs over time remains questionable, namely due to the heterogeneity of landscape characteristics inside and outside of NRs. This study (i) quantifies the role of 75 NRs in China in maintaining ESs (i.e., net primary production (NPP), soil conservation, sandstorm prevention and water yield) from 2000 to 2020, (ii) reveals the trade-offs/synergies, and (iii) identifies the main influencing factors of the ES effectiveness of NRs. The results show that more than 80% of NRs had positive ES effectiveness, which was greater in older NRs. For different ESs, effectiveness over time increases for NPP (E_NPP), soil conservation (E_SC) and sandstorm prevention (E_SP) but declines for water yield (E_WY). There is a clear synergistic relationship between E_NPP and E_SC. Moreover, the effectiveness of ESs is closely correlated with elevation, precipitation, and perimeter area ratio. Our findings can provide important information to support site selection and management of reserves to improve the delivery of critical ecosystem services.

Plant functional traits explain long-term differences in ecosystem services between artificial forests and natural grasslands.

Declining ecosystem services have prompted numerous studies aiming at developing more sustainable management practices for vegetation restoration. Advances in functional ecology indicate that the sustainable management of afforestation ecosystems should be performed based on plant functional traits, which provides pivotal knowledge for long-term sustainable vegetation restoration. Currently, the mechanism of how plant functional traits affect long term ecosystem services in restored areas is still unclear. This study investigates plant functional traits and the associated ecosystem services from artificial forestlands (Robinia pseudoacacia, Caragana korshinskii) and natural grasslands following different durations of vegetation restoration (10, 20, 30 and 40 years) in the Danangou watershed, a loess hilly-gully region in the Loess Plateau, China. The results showed that 1) the water conservation services of artificial forestlands first decreased and then increased over time, whereas the soil conservation service had an opposite trend; in turn, natural grassland led to a consistent increase in soil conservation and carbon sequestration services over time. 2) Artificial forestlands had greater soil conservation and carbon sequestration services than natural grassland but had lower water conservation services. 3) Leaves had a greater impact on carbon sequestration and water conservation services than did root length and root biomass density. 4) Root biomass density had a greater effect on soil conservation services than did leaf carbon content and soil organic matter. 5) Leaf carbon content, specific root length, and root biomass density had significant effects on the trade-off value between any two ecosystem services with increasing time after restoration of artificial forestland. 6) Specific leaf area had a greater effect on the trade-off values among the three services than did the other functional traits in the natural grassland. In arid ecosystems, natural grasslands are the best restoration strategy given their higher water conservation services. However, in soil erosion-affected areas, restoration through artificial forestlands is more appropriate. To mitigate the trade-offs between ecosystem services, it is recommended that artificial forestlands be thinned before the leaf carbon content, specific root length, and root biomass density reach a maximum (i.e., mature forestland).

GC-MS Silylation Derivative Method to Characterise Black BIC® Ballpoint 2-Phenoxyethanol Ratio Evaporation Profile-A Contribution to Ink Ageing Estimation.

One of the major challenges in forensic document analysis is estimating the age of ink deposition on a manually written document. The present work aims to develop and optimise a methodology, based on the evaporation of 2-phenoxyethanol (PE) over time, that can contribute to ink age estimation. A black BIC® Crystal Ballpoint Pen was purchased in a commercial area, and ink deposition began in September 2016 over 1095 days. For each ink sample, 20 microdiscs were subjected to n-hexane extraction in the presence of an internal standard (ethyl benzoate) followed by derivatisation with a silylation reagent. A gas chromatography-mass spectrometry (GC/MS) method was optimised for PE-trimethylsilyl (PE-TMS) to characterise the ageing curve. The developed method presented good linearity between 0.5 and 50.0 µg mL-1, as well as limits of detection and quantification of 0.026 and 0.104 µg mL-1, respectively. It was possible to characterise PE-TMS concentration over time, which reveals a two-phase decay behaviour. First, there was a substantial decline between the 1st and the 33rd day of deposition, followed a by a stabilisation of the signal, which allowed to detect the presence of PE-TMS up to 3 years. Two unknown compounds were also present and allowed to identify three dating time frames for the same ink stroke: (i) between time 0 and 33 days, (ii) between time 34 and 109 days, and (iii) more than 109 days. The developed methodology allowed to characterise the behaviour of PE over time and to establish a relative dating of three-time frames.

Using Glyphosate on Guarana Seedlings in the Amazon.

The seed yield of guarana (Paullinia cupana H.B.K. var. sorbilis) is affected by weeds. Management is difficult for Amazon farmers and ranchers, owing to the hot and humid climate prevailing in the region, which makes mechanical control inefficient and leads farmers to the decision to use herbicides. Herbicide damage to this species is unknown. The objective of this study was to evaluate glyphosate damage to the development and quality of guarana seedlings. The treatments consisted of glyphosate doses at concentrations of 0, 126, 252, 540, 1080, 2160 and 3240 g a.e. ha-1 and were evaluated for 60 days, in two applications. Analyses were performed for biometrics, seedling development, anthracnose and Injury characteristics. Glyphosate caused symptoms of Injury in all doses applied, but lower doses did not interfere with seedling growth and development. There was a correlation between anthracnose severity and increased glyphosate dose. When applied correctly, glyphosate can be an integrated weed management tool for use in guarana crops.

Connectivity approach in urban protected area management based on soil and vegetation chemical status.

The quality and vitality of cities largely depend on the design, management, and maintenance of green areas, including urban protected areas (UPAs), since they provide multiple benefits for the city. Due to urbanization and higher anthropogenic pressure, green areas are decreasing which directly affects natural habitats and biodiversity. This study aims to assess soil and vegetation chemical status in UPAs in the city of Belgrade, Serbia, and to understand how their distance from pollution hotspots affects soil and vegetation quality. Additionally, this paper considers the inclusion of soil and vegetation conditions in the urban protected areas management as a basis for introducing a connectivity approach to expand green infrastructure throughout the city. Chemical properties, the content of nutrients (C, N, P, and K), and microelements (Cr, Co, Ni, Cu, Zn, As, Cd, Sn, Pb, Zr, U, and Th) in soil and conifer needles were analyzed. Results showed that the distance of pollution hotspots does not affect nutrient and microelements concentrations in soil, i.e., they do not vary significantly between sites and do not exceed remediation intervention values. However, the microelements status of vegetation is affected since Cr, Cu, Zn, Sn, and Pb are higher in needles from trees from the city center. The state of soil and plant composition supports the establishment of a network of green corridors and should become a part of management strategies, thus helping biodiversity protection, climate change mitigation, and human well-being in the cities.

Reducing plant community variability and improving resilience for sustainable restoration of temperate grassland.

Grassland ecosystem is important for the realization of the global sustainable development goals (e.g. Goal 15) since it provides irreplaceable services for human beings, supporting human health and sustainable development. Most studies have focused on improving grassland restoration techniques, but less attention has been paid to grassland ecosystem stability in succession. Plant community stability of temperate grassland in arid and semi-arid regions is analyzed through 38 sampling sites in Inner Mongolia, China. The degradation succession sequence of grassland is established by principal component analysis, and the species diversity and functional diversity along degradation gradient analyzed by multivariate statistical analysis. The results show that (1) functional diversity has higher explanatory power for community stability than species diversity due to the functional dispersion of plant traits; (2) climate factors rather than grazing or soil control plant community diversity and stability at regional scale; (3) the resistance of plant community does not change in degradation succession, but the trade-off effect of stability components in different plant communities differ, such as the order of trade-off effects (e.g. community resilience (ET)＞community resistance (RT)＞structural variability (St)＞functional variability (Fu) in the community dominated by Stipa grandis, RT＞ET＞St＞Fu in Leymus chinensis community, St＞ET＞Fu＞RT in Stipa capillata community, RT＞St＞Fu＞ET in Artemisia frigida community, St＞Fu＞ET＞RT in Cleistogenes squarrosa community, and Fu＞St＞RT＞ET in Artemisia halodendron community); (4) grassland ecosystem with higher diversity shows greater resilience and lower variability than those with single species, which supports the established diversity hypothesis. Furthermore, sustainable grassland restoration should reduce community variability and improve resilience. These findings highlight the response of diversity to stability in temperate grassland and provide scientific support for grassland ecosystem protection and restoration.

Atrial cardiopathy predicts detection of atrial fibrillation in embolic stroke of undetermined source: real-life data.

OBJECTIVES: Atrial cardiopathy (AC) is more frequent in patients with embolic stroke of undetermined source (ESUS) than in patients with non-cardioembolic stroke. The aim of this work was to describe AC in patients with ESUS and to study its impact on detection of atrial fibrillation (AF) during follow-up. METHODS: This is an observational study of 123 consecutive ESUS patients and 55 ESUS patients from a previous cohort. AC was defined according to the presence of one or more of the following criteria: severe left atrial enlargement, p-wave terminal force in lead V1 > 5000 µVxms, and excessive premature atrial complexes. Unadjusted and adjusted survival analyses for the occurrence of AF and stroke or transient ischemic attack (TIA) were performed. Diagnostic performance of AC for the detection of AF was analyzed. RESULTS: Among 178 patients with ESUS, those with AC (42.7%) were older (p < 0.001), and more frequently had hypertension (p = 0.001) and lower total cholesterol levels (p = 0.001) than patients without AC. The detection of AF during follow-up (median 34 months, interquartile range = 12.8-64) was higher in patients with AC (hazard ratio = 7.00, 95% confidence interval = 2.01-24.39, p = 0.002). This association persisted after adjusting for age, arterial hypertension, and other vascular risk factors. The c-statistic for detection of AF during follow-up for AC was 0.719. There were no differences in stroke or TIA recurrence between groups with and without AC. DISCUSSION: ESUS patients with AC have different baseline clinical characteristics than patients without AC and have a higher detection of AF during follow-up.

Identifying barriers for nature-based solutions in flood risk management: An interdisciplinary overview using expert community approach.

The major event that hit Europe in summer 2021 reminds society that floods are recurrent and among the costliest and deadliest natural hazards. The long-term flood risk management (FRM) efforts preferring sole technical measures to prevent and mitigate floods have shown to be not sufficiently effective and sensitive to the environment. Nature-Based Solutions (NBS) mark a recent paradigm shift of FRM towards solutions that use nature-derived features, processes and management options to improve water retention and mitigate floods. Yet, the empirical evidence on the effects of NBS across various settings remains fragmented and their implementation faces a series of institutional barriers. In this paper, we adopt a community expert perspective drawing upon LAND4FLOOD Natural flood retention on private land network (https://www.land4flood.eu) in order to identify a set of barriers and their cascading and compound interactions relevant to individual NBS. The experts identified a comprehensive set of 17 barriers affecting the implementation of 12 groups of NBS in both urban and rural settings in five European regional environmental domains (i.e., Boreal, Atlantic, Continental, Alpine-Carpathian, and Mediterranean). Based on the results, we define avenues for further research, connecting hydrology and soil science, on the one hand, and land use planning, social geography and economics, on the other. Our suggestions ultimately call for a transdisciplinary turn in the research of NBS in FRM.

Sorption of benzo[a]pyrene by Chernozem and carbonaceous sorbents: comparison of kinetics and interaction mechanisms.

Benzo[a]pyrene (BaP) is a polycyclic aromatic hydrocarbon, highly persistent and toxic and a widespread environmental pollutant. Although various technologies have been developed to remove BaP from the environment, its sorption through solid matrixes has received increasing attention due to cost-effectiveness. The present research compares the adsorption capacity of Haplic Chernozem, granular activated carbon and biochar in relation to BaP from water solution. Laboratory experiments with different initial BaP concentrations in the liquid phase and different ratios of the solid and liquid phases show that Freundlich model describes well the adsorption isotherms of BaP by the soil and both sorbents. Moreover, the BaP isotherm sorption by the Haplic Chernozem is better illustrated by the Freundlich model than the Langmuir equation. The results reveal that the sorption capacity of the carbonaceous adsorbents at a ratio 1:20 (solid to liquid phases) is orders of magnitude higher (13 368 ng mL-1 of activated carbon and 3 578 ng mL-1 of biochar) compared to the soil (57.8 ng mL-1). At the ratio of 0.5:20, the adsorption capacity of the carbonaceous sorbents was 17-45 times higher than that of the soil. This is due to the higher pore volume and specific surface area of the carbonaceous sorbents than soil particles, assessed through scanning electron microscopy. The sorption kinetic of BaP by Chernozem was compared with the adsorption kinetics by the carbonaceous sorbents. Results indicate that the adsorption dynamic involves two steps. The first one is associated with a fast BaP adsorption on the large available surface and inside macro- and meso-pores of the sorbent particles of the granular activated carbon and biochar. Then, the adsorption is followed by a slower process of BaP penetration into the microporous space and/or redistribution into a hydrophobic fraction. The effectiveness of the sorption process depends on both the sorbent properties and the solvent competition. Overall, the granular activated carbon and biochar are highly effective adsorbents for BaP, whereas the Haplic Chernozem has a rather limited capacity to remove BaP from contaminated solutions.

Factors associated with childhood anaemia in Afro-descendant communities in Alagoas, Brazil.

OBJECTIVE: To investigate factors associated with anaemia in preschool children. DESIGN: A home survey was conducted in 2018. Anaemia in children (capillary blood Hb level < 110 g/l) was the outcome, and socio-economic, demographic and health factors of the mother and child were the independent variables. The measure of association was the prevalence ratio, and its 95 % CI was calculated using Poisson's regression with robust variance and hierarchical selection of independent variables. SETTING: Afro-descendants communities living in the state of Alagoas, northeast Brazil. PARTICIPANTS: Children aged 6-59 months and their mothers (n 428 pairs). RESULTS: The prevalence of child anaemia was 38·1 % (95 % CI 33·5, 42·7). The associated factors with child anaemia were male sex, age < 24 months, larger number of residents at home (> 4), relatively taller mothers (highest tertile) and higher z-score of BMI for age, after further adjustment for wealth index, vitamin A supplementation in the past 6 months and clinical visit in the last 30 d. CONCLUSIONS: The high prevalence of anaemia observed reveals a relevant public health problem amongst children under five from the quilombola communities of Alagoas. Considering the damage caused to health and multiplicity of risk factors associated with anaemia, the adoption of intersectoral strategies that act on modifiable risk factors and increase vigilance concerning those that are not modifiable becomes urgent.

Red Cell Distribution Width is Associated with 30-day Mortality in Patients with Spontaneous Intracerebral Hemorrhage.

BACKGROUND: Red cell distribution width (RDW) has been associated with mortality and outcome in a wide variety of non-neurological and neurological diseases, namely in myocardial infarction and acute ischemic stroke, and the reason for this is not completely understood. We aimed to investigate RDW as a potential prognostic marker in patients with intracerebral hemorrhage (ICH). METHODS: This is a retrospective study of consecutive patients with acute non-traumatic ICH admitted to a single center during a 4-year period. We reviewed individual clinical records to collect demographic and baseline information, including RDW at admission, 3-month functional status, and incidence of death during follow-up. Baseline computed tomography imaging was reviewed to classify the location of ICH, and to measure ICH volume and perihematomal edema volume. Patients were divided according to quartile distribution of RDW (RDW-Q1-4). RESULTS: The final study population consisted of 358 patients, median age 71 years (interquartile range [IQR] 60-80), 55% were male, and median Glasgow Coma Scale was 14 (IQR 10-15), with a mean follow-up of 17.6 months. Patients with higher RDW values were older (p = 0.003), more frequently presented with an active malignancy (p = 0.005), atrial fibrillation (p < 0.001), intraventricular hemorrhage (p = 0.048), and were anticoagulated (p < 0.001). Three-month functional independence was similar throughout RDW quartiles. RDW-Q4 was independently associated with increased 30-day mortality (adjusted odds ratio = 3.36, 95%CI = 1.48-7.62, p = 0.004), but not independently associated with increased mortality after 30 days (adjusted hazards ratio = 0.71, 95%CI = 0.29-1.73, p = 0.448). CONCLUSIONS: RDW is a robust and independent predictor of 30-day mortality in non-traumatic ICH patients, and further studies to understand this association are warranted.

Prognostic information of gaze deviation in acute ischemic stroke patients.

INTRODUCTION: Gaze deviation (GD) in acute ischemic stroke patients has been suggested to be associated with poor outcome and with the presence of large vessel occlusion. Our aim was to study the prognostic significance of GD in ischemic stroke patients submitted to acute revascularization treatments. METHODS: Retrospective single-center study of consecutive anterior circulation ischemic stroke patients submitted to thrombolysis and/or endovascular revascularization between 2007 and 2017. The groups of patients with and without GD were compared concerning baseline clinical and imagiological variables, functional outcome at 3 months, and survival at 1 year. RESULTS: Among a study population of 711 patients, 332 (46.7%) presented GD. Patients with GD were more frequently of female sex (p = 0.048), had higher baseline NIHSS scores (p < 0.001), had lower ASPECTS on baseline CT (p < 0.001), more frequently had ischemia of the right hemisphere (p < 0.001), presented higher NIHSS 24 hours after treatment (p < 0.001), and more frequently presented cardioembolic stroke (p = 0.003). In the unadjusted analyses, GD was associated with decreased 3-month functional independence and increased 1-month and 1 year mortality (p < 0.001). After adjustment for variables of interest, namely, for NIHSS 24 hours after treatment, GD was no longer associated with functional outcome or survival. CONCLUSIONS: GD in patients with acute ischemic stroke is associated with increased clinical and imagiological severity at baseline. However, in patients submitted to acute revascularization treatments, this does not appear to be independent predictor of functional outcome or survival.

Extraction Procedures for Hair Forensic Toxicological Analysis: A Mini-Review.

In forensic toxicology, drugs of abuse are routinely analyzed due to legal statute in medical or legal investigation, such as death cases, poisoning cases, and drug misuse, determining potential exposure to controlled substances. Despite the widespread use of blood and urine as matrices for forensic toxicological analysis, the use of hair samples has grown as the limitations associated with this matrix are overcome and new areas of application emerge. Hair provides several advantages over urine and blood, such as the easiness of sample collection and the ability to provide a retrospective analysis of drug consumption. Drug analysis in hair is following a path where less amount of sample has been needed to detect drugs of abuse. Improvement in sample preparation methods and lowering detection limits in instrumental analysis is providing forensic scientists with the tools to use drug analysis with hair as a routine approach in the forensic laboratory. Actually, besides the chronological exposition to a drug, hair may provide information about the day a chemical was used. This should become part of the standard information sent by forensic scientists to criminal investigators and courts. The aim of this review is to summon the extraction procedures used to perform forensic toxicological analysis in hair as well as the major advances in this field once a sample preparation step is critical and takes up most of the total analysis time.

The synthetic cannabinoid JWH-018 modulates Saccharomyces cerevisiae energetic metabolism.

Synthetic cannabinoids are a group of novel psychoactive substances with similar properties to Δ9-THC. Among the vast number of synthetic cannabinoids, designed to be tested in clinical trials, JWH-018 was the first novel psychoactive substance found in the recreational drug marketplace. The consumption of JWH-018 shows typical effects of CB1 agonists including sedation, cognitive dysfunction, tachycardia, postural hypotension, dry mouth, ataxia and psychotropic effects, but appeared to be more potent than Δ9-THC. However, studies on human cells have shown that JWH-018 toxicity depends on the cellular line used. Despite these studies, the underlying molecular mechanisms to JWH-018 action has not been clarified yet. To understand the impact of JWH-018 at molecular and cellular level, we used Saccharomyces cerevisiae as a model. The results showed an increase in yeast growth rate in the presence of this synthetic cannabinoid due to an enhancement in the glycolytic flux at expense of a decrease in pentose phosphate pathway, judging by 2D-Gel proteomic analysis, qRT-PCR experiments and ATP measurements. Overall, our results provide insights into molecular mechanisms of JWH-018 action, also indicating that Saccharomyces cerevisiae is a good model to study synthetic cannabinoids.

Candida spp. and phagocytosis: multiple evasion mechanisms.

Invasive fungal infections are a global health problem, mainly in hospitals, where year by year hundreds of patients die because of these infections. Commensal yeasts may become pathogenic to human beings, affecting mainly immunocompromised patients. During infectious processes, the immune system uses phagocytes to eliminate invader microorganisms. In order to prevent or neutralize phagocyte attacks, pathogenic yeasts can use virulence factors to survive, as well as to colonize and infect the host. In this review, we describe how Candida spp., mainly Candida albicans, interact with phagocytes and use several factors that contribute to immune evasion. Polymorphism, biofilm formation, gene expression and enzyme production mediate distinct functions such as adhesion, invasion, oxidative stress response, proteolysis and escape from phagocytes. Fungal and human cells have similar structures and mechanisms that decrease the number of potential targets for antifungal drugs. Therefore, research on host-pathogen interaction may aid in the discovery of new targets and in the development of new drugs or treatments for these diseases and thus to save lives.

Vascular White Matter Lesions in Young Adults: A Neurology Outpatient Clinic Registry.

INTRODUCTION: Although frequently assumed to be age-related changes, vascular white matter lesions (WML) are sometimes found in young adults. Etiology is usually attributed to sporadic small vessel disease; nevertheless, genetic disorders may also be implicated. We aimed to characterize the population of young adults with vascular WML in Neurology outpatient clinics. METHODS: Neurologists from 12 Portuguese hospitals were invited to include patients aged 18-55 years evaluated in consultation, with vascular WML on MRI, scoring II or III in the Fazekas scale. Central imaging validation was performed by 2 independent, blinded, Neuroradiologists. Demographic and clinical data were collected as well as results of investigations performed. RESULTS: During 2 years, 77 patients were included (mean age 47.7 years). Vascular risk factors were present in 88.3% patients (hypertension in 53.2%) and previous history of stroke in 36.4%. Patients without history of stroke were younger (46.6 ± 7.2 vs. 49.6 ± 3.9 years, p = 0.045) and had fewer vascular risk factors (p < 0.001). They were more frequently females (87.8 vs. 46.4%, p < 0.001), and headache (30.6 vs. 3.6%, p = 0.007), contrary to focal symptoms (16.3 vs. 53.6%, p = 0.001), was the most frequent reason of referral. Etiological investigations performed differed between Neurologists. A genetic disorder was identified in 6 out of 58 patients (CADASIL n = 5; COL4A1 n = 1). CONCLUSION: Young adults with vascular WML evaluated in Neurology outpatient clinics concentrate in the oldest age groups. Vascular risk factors should be screened carefully in this population. Among patients without history of stroke, females largely outweigh males. Diagnostic investigations performed do not follow a standardized protocol.