[Clinical profile and non-recreational methamphetamine abuse (shabu) among stroke patients in the Philippine population]. / Perfil clínico y abuso de metanfetamina no recreativa (shabú) entre los pacientes con ictus en la población filipina.

INTRODUCTION: Chronic non-recreational use of methamphetamine (shabu) is increasing among the Filipino population in Barcelona. The Asian population presents a different stroke pattern, with a higher incidence of haemorrhage, and different vascular risk factors and health behaviours. The objective of this study is to describe the stroke profile and incidence of methamphetamine use in patients of Filipino origin admitted to our centre. PATIENTS AND METHODS: Demographic data, vascular risk factors, clinical data and prognosis were recorded. Methamphetamine exposure was analysed in plasma samples collected on admission, which were then analysed by liquid chromatography-mass spectrometry. RESULTS: Of a total of 6,418 stroke patients, 73 (1.1%) were identified as being of Filipino origin. The mean age was 54.4 ± 12.1 years, 54% were male and the stroke was ischaemic in 64.4% of cases. Arterial hypertension was the main risk factor. Ten (13.7%) patients tested positive for methamphetamine and amphetamine. These results confirm recent substance use prior to the stroke, mostly in men (80%). In patients who were consumers, 60% had a haemorrhagic stroke, with a poor functional prognosis at three months in 55.6% of patients. CONCLUSIONS: In our setting, patients of Filipino ethnicity admitted for stroke related to the consumption of shabu belonged a younger age bracket, with a lower prevalence of vascular risk factors and a predominance of the haemorrhagic subtype. Methamphetamine testing in Filipino stroke patients is recommended due to the high prevalence of methamphetamine use in our country.

TITLE: Perfil clínico y abuso de metanfetamina no recreativa (shabú) entre los pacientes con ictus en la población filipina.Introducción. En la población filipina de Barcelona está aumentando el consumo crónico no recreativo de metanfetaminas (shabú). La población asiática presenta un patrón de ictus diferente, con mayor incidencia de hemorragias, y diferentes factores de riesgo vascular y conductas de salud. El objetivo es describir el perfil de ictus e incidencia de consumo de metanfetaminas en pacientes de origen filipino ingresados en nuestro centro. Pacientes y métodos. Se registraron datos demográficos, factores de riesgo vascular, datos clínicos y pronóstico. Se analizó la exposición a metanfetamina en muestras de plasma recogidas en el ingreso, que se analizaron por cromatografía líquida-espectrometría de masas. Resultados. Del total de 6.418 pacientes con ictus, se identificó a 73 pacientes filipinos (1,1%). La edad media era de 54,4 ± 12,1 años, el 54% eran hombres y el ictus era isquémico en el 64,4%. La hipertensión arterial fue el principal factor de riesgo. Diez (13,7%) pacientes dieron positivo a metanfetamina y anfetamina. Estos resultados confirman un consumo reciente de sustancias previo al ictus, principalmente en hombres (80%). En pacientes consumidores, un 60% presentaba un ictus hemorrágico, con mal pronóstico funcional a tres meses en el 55,6% de los pacientes. Conclusiones. En nuestro medio, los pacientes de etnia filipina ingresados por ictus en relación con consumo de shabú presentaron un perfil de edad más joven, con menor prevalencia de factores de riesgo vascular y predominio del subtipo hemorrágico. Se recomienda la determinación de metanfetamina en los pacientes filipinos con ictus debido a la alta prevalencia del consumo de metanfetamina en nuestro país.

Development and patient acceptance of Preanestes@s, a web-based application and electronic questionnaire for preoperative assessment. A prospective cohort study.

BACKGROUND AND OBJECTIVES: We describe the development of Preanestes@s, a web-based application for preoperative assessment, which incorporates PreQuest, a smart computer-based self-assessment questionnaire for the automated management of information. Preanestes@s potentially enables remote non-telephonic preoperative assessment. The main objective of this work was the identification of factors that independently predict adequate completion of PreQuest. As a secondary objective, we assessed patient experience using the application. MATERIAL AND METHODS: To assess the influence of patient conditions on PreQuest completion, our sample included 880 adult patients scheduled to undergo surgery at our institution between February 2020 and February 2021. We evaluated patient satisfaction and acceptability with the use of the application and PreQuest. RESULTS: A total of 573 participants (65.1%) successfully completed the PreQuest. Age below 65 years and higher educational attainment were identified as independent predictors for PreQuest completion (p = 0.04 and p = 0.001, respectively). Most (89.4%) participants agreed that Preanestes@s was intuitive and easy to use, with over 85% showing high levels of acceptance of PreQuest prototype's communication improvement and ease of use. The final version of Preanestes@s and PreQuest was evaluated by 218 participants, many of whom (>74%) affirmed its ease of use. CONCLUSIONS: The use of Preanestes@s for preoperative assessment is supported by high levels of satisfaction with the prototype and by an eQuest completion rate greater than 65% in a non-selective population. In our sample, younger age and higher education attainment predicted higher rates PreQuest completion. Trial registration number NCT04259268.

Migraine-Associated Common Genetic Variants Confer Greater Risk of Posterior vs. Anterior Circulation Ischemic Stroke☆.

OBJECTIVE: To examine potential genetic relationships between migraine and the two distinct phenotypes posterior circulation ischemic stroke (PCiS) and anterior circulation ischemic stroke (ACiS), we generated migraine polygenic risk scores (PRSs) and compared these between PCiS and ACiS, and separately vs. non-stroke control subjects. METHODS: Acute ischemic stroke cases were classified as PCiS or ACiS based on lesion location on diffusion-weighted MRI. Exclusion criteria were lesions in both vascular territories or uncertain territory; supratentorial PCiS with ipsilateral fetal posterior cerebral artery; and cases with atrial fibrillation. We generated migraine PRS for three migraine phenotypes (any migraine; migraine without aura; migraine with aura) using publicly available GWAS data and compared mean PRSs separately for PCiS and ACiS vs. non-stroke control subjects, and between each stroke phenotype. RESULTS: Our primary analyses included 464 PCiS and 1079 ACiS patients with genetic European ancestry. Compared to non-stroke control subjects (n=15396), PRSs of any migraine were associated with increased risk of PCiS (p=0.01-0.03) and decreased risk of ACiS (p=0.010-0.039). Migraine without aura PRSs were significantly associated with PCiS (p=0.008-0.028), but not with ACiS. When comparing PCiS vs. ACiS directly, migraine PRSs were higher in PCiS vs. ACiS for any migraine (p=0.001-0.010) and migraine without aura (p=0.032-0.048). Migraine with aura PRS did not show a differential association in our analyses. CONCLUSIONS: Our results suggest a stronger genetic overlap between unspecified migraine and migraine without aura with PCiS compared to ACiS. Possible shared mechanisms include dysregulation of cerebral vessel endothelial function.

Gut microbiota and voluntary alcohol consumption.

Alcohol is part of the usual diet of millions of individuals worldwide. However, not all individuals who drink alcohol experience the same effects, nor will everyone develop an alcohol use disorder. Here we propose that the intestinal microbiota (IMB) helps explain the different consumption patterns of alcohol among individuals. 507 humans participated in this study and alcohol consumption and IMB composition were analyzed. On the other hand, in 80 adult male Wistar rats, behavioral tests, alcohol intoxication, fecal transplantation, administration of antibiotics and collection of fecal samples were performed. For identification and relative quantification of bacterial taxa was used the bacterial 16 S ribosomal RNA gene. In humans, we found that heavy episodic drinking is associated with a specific stool type phenotype (type 1, according to Bristol Stool Scale; p < 0.05) and with an increase in the abundance of Actinobacteria (p < 0.05). Next, using rats, we demonstrate that the transfer of IMB from alcohol-intoxicated animals causes an increase in voluntary alcohol consumption in transplant-recipient animals (p < 0.001). The relative quantification data indicate that the genus Porphyromonas could be associated with the effect on voluntary alcohol consumption. We also show that gut microbiota depletion by antibiotics administration causes a reduction in alcohol consumption (p < 0.001) and altered the relative abundance of relevant phyla such as Firmicutes, Bacteroidetes or Cyanobacteria (p < 0.05), among others. Benjamini-Hochberg false discovery rate (FDR) correction was performed for multiple comparisons. These studies reveal some of the consequences of alcohol on the IMB and provide evidence that manipulation of IMB may alter voluntary alcohol consumption.

Biological Age Acceleration Is Lower in Women With Ischemic Stroke Compared to Men.

BACKGROUND: Stroke onset in women occurs later in life compared with men. The underlying mechanisms of these differences have not been established. Epigenetic clocks, based on DNA methylation (DNAm) profiles, are the most accurate biological age estimate. Epigenetic age acceleration (EAA) measures indicate whether an individual is biologically younger or older than expected. Our aim was to analyze whether sexual dichotomy at age of stroke onset is conditioned by EAA. METHODS: We used 2 DNAm datasets from whole blood samples of case-control genetic studies of ischemic stroke (IS), a discovery cohort of 374 IS patients (N women=163, N men=211), from GRECOS (Genotyping Recurrence Risk of Stroke) and SEDMAN (Dabigatran Study in the Early Phase of Stroke, New Neuroimaging Markers and Biomarkers) studies and a replication cohort of 981 IS patients (N women=411, N men=570) from BASICMAR register. We compared chronological age, 2 DNAm-based biomarkers of aging and intrinsic and extrinsic epigenetic age acceleration EAA (IEAA and extrinsic EAA, respectively), in IS as well as in individual IS etiologic subtypes. Horvath and Hannum epigenetic clocks were used to assess the aging rate. A proteomic study using the SOMAScan multiplex assay was performed on 26 samples analyzing 1305 proteins. RESULTS: Women present lower Hannum-extrinsic EAA values, whereas men have higher Hannum-extrinsic EAA values (women=-0.64, men=1.24, P=1.34×10-2); the same tendency was observed in the second cohort (women=-0.57, men=0.79, P=0.02). These differences seemed to be specific to cardioembolic and undetermined stroke subtypes. Additionally, 42 blood protein levels were associated with Hannum-extrinsic EAA (P<0.05), belonging to the immune effector process (P=1.54×10-6) and platelet degranulation (P<8.74×10-6) pathways. CONCLUSIONS: This study shows that sex-specific underlying biological mechanisms associated with stroke onset could be due to differences in biological age acceleration between men and women.

Prospective epidemiological study of basketball injuries during one competitive season in professional and amateur Spanish basketball.

INTRODUCTION: There are few Spanish epidemiological studies of basketball injuries, even though it is the second most played sport and the leading sport played by females in Spain. POPULATION: We studied 117 male and female basketball players from ten amateur or professional teams from four leagues in the 2014-2015 season. RESULTS: There were 11.6 injuries per 1,000 hours of sporting activity, 9.6 injuries per 1,000 hours of training and 47.3 injuries per 1,000 hours of competition. The rate of injuries requiring downtime was 2.99 per 1,000 hours of training, 41.7 per 1,000 hours of competition and 4.1 per 1,000 hours of sporting activity overall. No significant differences were found in the incidence of injuries between leagues, but a higher incidence by season was found in teams participating in international competitions, due to the increased competition time. The ankle was the main site of injuries causing ≥ 8 days of downtime and knee injuries the site of those causing ≥ 29 days of downtime. The most frequent injuries were sprains, bruises, and muscle overloads and 63.8% of players had ≥ 1 potentially-recurring injury. The most prevalent injuries were ankle sprains (50%), thigh muscle injuries (12.2%) and knee tendinitis (7.4%). The only significant predisposing factor for injury was recurrent injury (adjusted OR 1.93, 95% CI 1.029-3.62). Age, sex, height, weight, position, body mass index, and professional/amateur competition were not significantly associated with the number of injuries or ≥ 7 days downtime in the multivariate analysis. CONCLUSION: Preventive measures should be applied to the team as a whole at an early age, since recurrent injuries only explained a small percentage of the total injuries.

Alcohol mixed with energy drinks: what about taurine?

RATIONALE: Since energy drinks (EDs) were marketed to the general public as recreational and soft drinks, mixing these with alcohol has become a popular practice, especially in the younger population. Alcohol mixed with EDs (AmEDs) is a particularly alarming combination, given the evidence that consistently associate these drinks with increased risk behaviours and greater alcohol consumption. Caffeine and taurine are commonly found in EDs. In contrast to caffeine, the studies on taurine psychoactive properties and how this amino acid influences ethanol intake alone or in combination with caffeine are not so numerous. OBJECTIVES: We summarised relevant and available data on the studies focusing on taurine as a psychoactive agent and its influence on ethanol (EtOH)-induced behaviours. Given the increased risk that represents mixing alcohol with energy drinks, we put emphasis on the research exploring the impact of these combinations on motivated behaviour towards EtOH consumption. RESULTS: The research on taurine properties on motivated behaviour towards EtOH consumption is limited, and mostly all done in combination with caffeine or other molecules. This makes it difficult to elucidate the effect of this amino acid when combined with alcohol. CONCLUSIONS: Incomplete understanding of the properties and effects of AmEDs is unavoidable until more studies are performed on the influence of taurine on motivation to consume alcohol. Taurine should be further explored, particularly in regard to its potential beneficial applications, motivational properties and synergies with other psychoactive ingredients (i.e. caffeine).

How unsaturated fatty acids and plant stanols affect sterols plasma level and cellular membranes? Review on model studies involving the Langmuir monolayer technique.

The Langmuir monolayer technique has long been known for its usefulness to study the interaction between molecules and mimic cellular membranes to understand the mechanism of action of biologically relevant molecules. In this review we summarize the results that provided insight into the potential mechanism for lowering the plasma level of cholesterol by hypocholesterolemic substances (unsaturated fatty acids (UFAs) and phytocompounds) - in the aspect of prevention of atherosclerosis - and their effects on model biomembranes. The results on UFAs/cholesterol (oxysterols) interactions indicate that these systems are miscible and strongly interacting, contrary to immiscible systems containing saturated fatty acids. Lowering of cholesterol plasma level by UFAs was attributed to the strong affinity between UFAs and sterols, resulting in the formation of high stability complexes, in which sterols were bound and eliminated from the body. Studies on the effect of UFAs and plant sterols/stanols on simplified biomembranes (modeled as cholesterol/DPPC system) indicated that the studied hypocholesterolemic substances modify the biophysical properties of model membrane, affecting its fluidity and interactions between membrane components. Both UFAs and plant sterols/stanols were found to loosen interactions between DPPC and cholesterol and decrease membrane rigidity caused by the excess cholesterol in biomembrane, thus compensating strong condensing effect of cholesterol and restoring proper membrane fluidity, which is of utmost importance for normal cells functioning. The agreement between model - in vitro - studies and biological results prove the usefulness of the Langmuir monolayer technique, which helps in understanding the mode of action of biologically relevant substances.

Correction to: Features of intracranial hemorrhage in cerebral venous thrombosis.

The original version of this article unfortunately contained mistakes. The correct information is given below.

Features of intracranial hemorrhage in cerebral venous thrombosis.

BACKGROUND: Cerebral venous thrombosis (CVT) is associated with intracranial hemorrhage. AIM: To identify clinical and imaging features of CVT-associated intracranial hemorrhage. We hypothesized that higher clot burden would be associated with a higher risk of intracranial hemorrhage. METHODS: We performed a retrospective analysis of an international, multicenter cohort of patients with confirmed cerebral venous thrombosis who underwent computed tomography within 2 weeks of symptom onset. Clinical and imaging features were compared between patients with and without intracranial hemorrhage. Clot burden was assessed by counting the number of thrombosed venous sinuses and veins on confirmatory imaging. RESULTS: We enrolled 260 patients from 10 institutions in Europe and Mexico. The mean age was 42 years and 74% were female. Intracranial hemorrhage was found in 102 (39%). Among them parenchymal hemorrhage occurred in 64 (63%), in addition, small juxta-cortical hemorrhage was found in 30 (29%), subarachnoid hemorrhage in 24 (24%) and subdural hemorrhage in 11 (11%). Multiple concomitant types of hemorrhage occurred in 23 (23%). Older age and superior sagittal thrombosis involvement were associated with presence of hemorrhage. The number of thrombosed venous sinuses was not associated with intracranial hemorrhage (median number IQRInterquartile ratio] of sinuses/veins involved with hemorrhage 2 (1-3) vs. 2 (1-3) without hemorrhage, p = 0.4). CONCLUSION: The high rate of intracranial hemorrhage in cerebral venous thrombosis is not explained by widespread involvement of the venous sinuses. Superior sagittal sinus involvement is associated with higher bleeding risk.

A parsimonious score with a free web tool for predicting disability after an ischemic stroke: the Parsifal Score.

BACKGROUND: Most of the models to predict prognosis after an ischemic stroke include complex mathematical equations or too many variables, making them difficult to use in the daily clinic. We want to predict disability 3 months after an ischemic stroke in an independent patient not receiving recanalization treatment within the first 24 h, using a minimum set of variables and an easy tool to facilitate its implementation. As a secondary aim, we calculated the capacity of the score to predict an excellent/devastating outcome and mortality. METHODS: Eight hundred and forty-four patients were evaluated. A multivariable ordinal logistic regression was used to obtain the score. The Modified Rankin Scale (mRS) was used to estimate disability at the third month. The results were replicated in another independent cohort (378 patients). The "polr" function of R was used to perform the regression, stratifying the sample into seven groups with different cutoffs (from mRS 0 to 6). RESULTS: The Parsifal score was generated with: age, previous mRS, initial NIHSS, glycemia on admission, and dyslipidemia. This score predicts disability with an accuracy of 80-76% (discovery-replication cohorts). It has an AUC of 0.86 in the discovery and replication cohort. The specificity was 90-80% (discovery-replication cohorts); while, the sensitivity was 64-74% (discovery-replication cohorts). The prediction of an excellent or devastating outcome, as well as mortality, obtained good discrimination with AUC > 0.80. CONCLUSIONS: The Parsifal Score is a model that predicts disability at the third month, with only five variables, with good discrimination and calibration, and being replicated in an independent cohort.

Searching for Rheological Conditions for FFF 3D Printing with PVC Based Flexible Compounds.

Rheology is proposed as a tool to explore plasticized poly(vinyl chloride) (PVC) formulations to be used in the fused filament fabrication (FFF) 3D printing process and so manufactures flexible and ductile objects by this technique. The viscoelastic origin of success/failure in FFF of these materials is investigated. The analysis of buckling of the filament is based on the ratio between compression modulus and viscosity, but for a correct approach the viscosity should be obtained under the conditions established in the nozzle. As demonstrated by small amplitude oscillatory shear (SAOS) measurements, PVC formulations have a crystallites network that provokes clogging in the nozzle. This network restricts printing conditions, because only vanishes at high temperatures, at which thermal degradation is triggered. It is observed that the analysis of the relaxation modulus G(t) is more performing than the G″/G' ratio to get conclusions on the quality of layers welding. Models printed according to the established conditions show an excellent appearance and flexibility, marking a milestone in the route to obtain flexible objects by FFF.

Ultra-early continuous cardiac monitoring improves atrial fibrillation detection and prognosis of patients with cryptogenic stroke.

BACKGROUND AND PURPOSE: Subclinical atrial fibrillation (AF) is known to underlie a number of cases of cryptogenic stroke (CrS). However, there is need to define the most effective strategy for AF detection. The diagnostic usefulness was analysed of a strategy based on ultra-early continuous monitoring in patients with CrS in terms of AF detection, oral anticoagulation treatment and stroke recurrence, in comparison to a standard outpatient strategy. METHODS: Patients with ischaemic stroke of undetermined origin and confirmed to be cryptogenic after extensive work-up were searched for AF with (i) a conventional strategy (historical cohort, n = 101) with serial electrocardiograms and 24-h Holter monitoring or (ii) an ultra-early monitoring strategy with insertable cardiac monitor (ICM) implanted before discharge (prospective cohort, n = 90). AF episodes lasting >1 min, anticoagulant treatment and stroke recurrence were recorded. RESULTS: During admission, AF was similarly detected in both cohorts (24% of patients). After discharge (mean follow-up 30 ± 10 months), AF detection rates were 17/80 (21.3%) and 38/65 (58.5%) for patients in the conventional versus the ultra-early ICM group (P < 0.001). Up to 41% of AF cases in the ICM cohort were detected within the first month. Oral anticoagulation was initiated in 37.6% versus 65.5% (P < 0.001) and stroke recurrence was recorded in 10.9% versus 3.3% (P 0.04) in the conventional versus the ICM cohort. CONCLUSIONS: Pre-discharge ICM implant allows detection of AF during follow-up in up to 58% of selected patients with CrS. Compared to a conventional strategy, ultra-early ICM implant results in higher anticoagulation rates and a decrease in stroke recurrence.

Detailed phenotyping of posterior vs. anterior circulation ischemic stroke: a multi-center MRI study.

OBJECTIVE: Posterior circulation ischemic stroke (PCiS) constitutes 20-30% of ischemic stroke cases. Detailed information about differences between PCiS and anterior circulation ischemic stroke (ACiS) remains scarce. Such information might guide clinical decision making and prevention strategies. We studied risk factors and ischemic stroke subtypes in PCiS vs. ACiS and lesion location on magnetic resonance imaging (MRI) in PCiS. METHODS: Out of 3,301 MRIs from 12 sites in the National Institute of Neurological Disorders and Stroke (NINDS) Stroke Genetics Network (SiGN), we included 2,381 cases with acute DWI lesions. The definition of ACiS or PCiS was based on lesion location. We compared the groups using Chi-squared and logistic regression. RESULTS: PCiS occurred in 718 (30%) patients and ACiS in 1663 (70%). Diabetes and male sex were more common in PCiS vs. ACiS (diabetes 27% vs. 23%, p < 0.05; male sex 68% vs. 58%, p < 0.001). Both were independently associated with PCiS (diabetes, OR = 1.29; 95% CI 1.04-1.61; male sex, OR = 1.46; 95% CI 1.21-1.78). ACiS more commonly had large artery atherosclerosis (25% vs. 20%, p < 0.01) and cardioembolic mechanisms (17% vs. 11%, p < 0.001) compared to PCiS. Small artery occlusion was more common in PCiS vs. ACiS (20% vs. 14%, p < 0.001). Small artery occlusion accounted for 47% of solitary brainstem infarctions. CONCLUSION: Ischemic stroke subtypes differ between the two phenotypes. Diabetes and male sex have a stronger association with PCiS than ACiS. Definitive MRI-based PCiS diagnosis aids etiological investigation and contributes additional insights into specific risk factors and mechanisms of injury in PCiS.

New look for an old molecule - Solid/solid phase transition in cholesterol monolayers.

Surface pressure (π) - molecular area (A) isotherms of cholesterol were precisely measured to get insight into the orientation of molecules in Langmuir monolayers, which allowed to obtain detailed information on their phase behaviour. This was possible from the detailed analysis of the interfacial compressibility modulus versus surface pressure (Cs-1- π) plots (obtained from the experimental surface pressure, π - area, A isotherms) and films thickness measurements (applying Brewster angle microscope, BAM) complemented with polarization-modulation infrared reflection-absorption spectroscopy (PM-IRRAS). At first glance, the isotherm for cholesterol is characterized by the major slope change of surface pressure versus area per molecule. However, a more detailed analysis showed the presence of a discontinuity and slope change both upon the compression and expansion of the monolayer. This discontinuity is more accurately reflected in the Cs-1- π plot as a pseudo-plateau visible at π values between approximately 5 and 10 mN/m. This plateau was found to be temperature-dependent. Also, film thickness versus area plot (th-A) exhibits a pseudo-plateau in this region of surface pressures, in which the monolayer thickness increased gradually from 1.15 nm to 1.5 nm. Interestingly, although cholesterol has been intensively investigated in Langmuir monolayers, the existence of such a plateau have been overlooked previously. By linking experimental thickness values with theoretical molecular conformations, we have identified the presence of this plateau to the solid-solid (S-S') second-order transition. Using 2D analog of Clausius-Clapeyron equation, the thermodynamic functions (ΔH and ΔS) for this transition have been calculated. Based on monolayer experiments, the orientation of molecules in both solid phases was assumed to differ in the orientation of short alkyl chain attached to C17, which has additionally been confirmed with PM-IRRAS analysis.

Knowing Patients Better After a Stroke and Secondary Prevention.

The habits and lifestyles are the fundamental factors in the control of cardiovascular risk. Patients who have had a cerebrovascular accident (CVA) have a high risk of having a new event with similar characteristics. The exponentially growing success, penetration and adherence of the new communication technologies, based on applications (APPs), allows to use them to obtain information and influence the risk factors. We propose that empowering patients in their disease can make a more efficient management of it. For this reason, we designed and developed a system which integrates a mobile application and a web application. This system also makes use of peripheral devices to monitor patients and allow the automatic acquisition of information to enable the characterization of this kind of patients in relation to habits and lifestyle. At the same time, the system can also empower these patients with their disease to do secondary prevention.

Interactions of cholesterol and 7­ketocholesterol with unsaturated fatty acids of different unsaturation degree - The monolayer study.

Unsaturated fatty acids (UFAs) are known to lower the level of sterols in blood, which accounts for their cardioprotective effect. To understand the molecular basis of this effect, Langmuir monolayer studies have been performed. A series of UFAs differing in the length of the fatty acid chain and the number of double bonds (oleic acid, OA; linoleic acid, LA; stearidonic acid, SDA; eicosanoic acid, EA) were mixed with cholesterol and its more toxic oxidized derivative, 7­ketocholesterol (7-KC), abundantly present in atheroma plaques. Strong attractive UFA-sterol interactions were attributed to the formation of "surface complexes", in which sterol molecules are bound, thereby reducing the amount of free sterol molecules. It has been found that strength of interactions increases with the degree of unsaturation of the acyl chain in UFA molecule. The most attractive interactions correspond to mixtures with SDA containing 70 mol% of 7-KC and 50 mol% of cholesterol. In both cases, the formation of high stability complexes of, respectively, 2:1 and 1:1 sterol/SDA stoichiometry has been proposed. Other complexes of lower stability and 1:2 stoichiometry were postulated for chol (or 7-KC)/LA systems. The complexes of the lowest stability correspond to chol (or 7-KC) mixtures with OA and EA of 1:1 stoichiometry. In all the cases, the interactions of 7-KC with UFAs are more energetically favorable versus cholesterol. The elongation of the hydrophobic chain of UFAs decreased the interactions with the studied sterols. The obtained results can be related to different conformations of the fatty acids chains.

Description of stroke mimics after complete neurovascular assessment. / Estudio descriptivo de los stroke mimics después de un estudio neurovascular completo.

INTRODUCTION: A considerable percentage of events initially diagnosed as ischaemic stroke have non-cerebrovascular causes; these are called stroke mimics (SM). Currently available evidence about these events is heterogeneous and comes from studies with small samples. OBJECTIVE: The purpose of our study is to identify conditions that may present as SM, define their epidemiological and clinical characteristics, and determine the percentage of cases of SM treated with intravenous fibrinolysis. METHODS: Prospective study including all patients admitted to a tertiary university hospital between June 2005 and April 2015 with a diagnosis of acute stroke. We analysed demographic data, cardiovascular risk factors, time from code stroke activation to admission, stroke severity (NIHSS), final destination after discharge, degree of disability (mRS), and treatment. We compared SM and ischaemic strokes. We ruled out patients with intracranial haemorrhage, subarachnoid haemorrhage, or other causes of SM that may be detected on the baseline CT scan. RESULTS: Four hundred four of the 4,570 included patients (8.8%) were found to have SM. Patients with SM were younger (70.3 vs. 74, P<.0001), less likely to exhibit cardiovascular risk factors and atrial fibrillation (13 vs. 34%, P<.0001), scored lower on the NIHSS at baseline (2 vs. 4, P<.0001), and included fewer cases of aphasia (9.4 vs. 19.6%, P<.02) and dysphagia (1.2 vs. 17%, P<.0001) than patients with stroke. SM caused fewer code stroke activations (28 vs. 40%, P<.0001). Patients with SM required shorter hospital stays (4.9 vs. 7.8 days, P<.0001), were less frequently admitted to the stroke unit (47 vs. 60%, P<.0001) and more frequently discharged home (95 vs. 62%, P<.0001), and had better outcomes (mRS scores 0-2; 76 vs. 54%, P<.0001). Intravenous fibrinolysis was administered to 4.7% of these patients. Epileptic seizures were the most frequent cause of SM (26%). CONCLUSIONS: In our sample, 8.8% of all diagnoses of ischaemic stroke were SM. These events have different demographic, clinical, and prognostic characteristics; epilepsy is the most common aetiology. Despite receiving specialised emergency care, 19 patients with SM (4.7%) were treated with intravenous fibrinolysis.

Adult-onset hypothyroidism increases ethanol consumption.

RATIONALE: Only in Europe it can be estimated that more than 20 million of people would be affected by hypothyroidism in some moment of their life. Given that ethanol consumption is so frequent, it would be reasonable to ask what the consequences of ethanol consumption in those individuals affected by hypothyroidism are. OBJECTIVES: To study the interaction between hypothyroidism and ethanol consumption. METHODS: We study ethanol consumption in a rat model of methyl-mercaptoimidazole-induced-adult-onset hypothyroidism and thyroid T4/T3 hormone supplementation. Also, we studied the effects of ethanol on motor activity, memory, and anxiety. RESULTS: We found that hypothyroidism increased the voluntary ethanol consumption and that this was enhanced by thyroid hormone supplementation. Hypothyroidism was associated with motor hyperactivity which was prevented either by T4/T3 supplementation or ethanol. The relationship between hypothyroidism, ethanol, and anxiety was more complex. In an anxiogenic context, hypothyroidism and T4/T3 supplementation would increase immobility, an anxiety-like behavior, while in a less anxiogenic context would decrease rearing, a behavior related to anxiety. Regarding memory, acute ethanol administration did not alter episodic-like memory in hypothyroid rats. Gene expression of enzymes involved in the metabolism of ethanol, i.e., Adh1 and Aldh2, were altered by hypothyroidism and T4/T3 supplementation. CONCLUSIONS: Our results suggest that hypothyroid patients would need personalized attention in terms of ethanol consumption. In addition, they point that it would be useful to embrace the thyroid axis in the study of ethanol addiction, including as a possible therapeutic target for the treatment of alcoholism and its comorbid disorders.

Effects of saturated and polyunsaturated fatty acids on interactions with cholesterol versus 7-ketocholesterol in Langmuir monolayers and their potential biological implications.

In this work the Langmuir monolayer technique was used to study interactions between cholesterol (chol) and 7-ketocholesterol (7-KC) with saturated (arachidic acid, AA) and polyunsaturated fatty acids (PUFAs) (ω-3 α-linolenic acid, α-LA,and ω-6 γ- linolenic, γ-LA) in order to get insight into their potential role in atherosclerosis. For this study, surface pressure (π)-area (A) isotherms, compressibility modulus (Cs-1) versus π plots, Brewster angle microscopy (BAM) images and excess functions (Aexc and ΔGexc) were analysed. Different behaviour has been observed. For cholesterol/AA mixed monolayers, components immiscibility occurs, whatever the surface pressure or the mixtures composition is, whereas for the 7-KC/AA mixed system, ideal behaviour was observed at low and high surface pressures for all the investigated compositions. However, the remaining mixed studied systems (sterol/PUFA) exhibit negative deviations from the ideality, although some differences do occurr. The magnitude of these deviations depend on the kind of a PUFA (for ω-3 PUFA greater than for ω-6) - attributed to the different geometry of their acyl chains- and the type of a sterol (for 7-KC greater than for cholesterol).The strength of attractive interactions followed the order: chol/ γ-LA <7-KC/γ-LA < chol/α-LA < 7-KC/ α-LA, postulating the formation of stable complexes of 1:2 stoichiometry for 7-KC/α-LA mixed monolayers and 1:1 stoichiometry for chol/α-LA mixed films. For 7-KC/γ-LA system, the formation of a low stability complex of 2:1 stoichiometry was suggested. The existence of these complexes can play an important role in diminishing the circulating sterols in the blood stream, thus decreasing the probability of atherosclerotic plaques formation.