Discovering trends in the Lewis acidity of beryllium and magnesium hydrides and fluorides with increasing clusters size.

We have reported in the last years the strong effect that Be- and Mg-containing Lewis acids have on the intrinsic properties of typical bases, which become acids upon complexation. In an effort to investigate these changes when the Be and Mg derivatives form clusters of increasing size, we have examined the behavior of the (MX2)n (M = Be, Mg; X = H, F; n = 1, 2, 3) clusters when they interact with ammonia, methanimine, hydrogen cyanide and pyridine, and with their corresponding deprotonated forms. The complexes obtained at the M06-2X/aug-cc-pVTZ level were analyzed using the MBIE energy decomposition formalism, in parallel with QTAIM, ELF, NCIPLOT and AdNDP analyses of their electron density. For n = 1 the interaction enthalpy for the different families of monomers, Be (Mg) hydrides and Be (Mg) fluorides, follows the same trend as the intrinsic basicity of the base that interacts with them. This interaction is greatly reinforced after the deprotonation of the base, resulting in a significant enhancement of the intrinsic acidity of the corresponding MX2-Base complex. For (MX2)2 clusters a further reinforcement of the interaction with the base is observed, this reinforcement being again larger for the deprotonated complexes. However, the concomitant increase of their intrinsic acidity is one order of magnitude larger for hydrides than for fluorides. Unexpectedly, the cyclic conformers (MX2)3, which are more unstable than the linear ones, become the global minima after association with the base and the same is true for the deprotonated complex. Accordingly, a further increase of the intrinsic acidity of the (MX2)3-Base complexes with respect to the (MX2)2-Base ones is observed. This effect is maximum for (MgF2)3 clusters, to the point that the (MgF2)3-Base complexes become more acidic than nitric acid, the extreme case being the cluster (MgF2)3-NCH, whose acidity is higher than that of perchloric acid.

Pharmacological preclinical comparison of tenecteplase and alteplase for the treatment of acute stroke.

Alteplase (rtPA) remains the standard thrombolytic drug for acute ischemic stroke. However, new rtPA-derived molecules, such as tenecteplase (TNK), with prolonged half-lives following a single bolus administration, have been developed. Although TNK is currently under clinical evaluation, the limited preclinical data highlight the need for additional studies to elucidate its benefits. The toxicities of rtPA and TNK were evaluated in endothelial cells, astrocytes, and neuronal cells. In addition, their in vivo efficacy was independently assessed at two research centers using an ischemic thromboembolic mouse model. Both therapies were tested via early (20 and 30 min) and late administration (4 and 4.5 h) after stroke. rtPA, but not TNK, caused cell death only in neuronal cultures. Mice were less sensitive to thrombolytic therapies than humans, requiring doses 10-fold higher than the established clinical dose. A single bolus dose of 2.5 mg/kg TNK led to an infarct reduction similar to perfusion with 10 mg/kg of rtPA. Early administration of TNK decreased the hemorrhagic transformations compared to that by the early administration of rtPA; however, this result was not obtained following late administration. These two independent preclinical studies support the use of TNK as a promising reperfusion alternative to rtPA.

Systemic biomarker associated with poor outcome after futile reperfusion.

BACKGROUND: Successful recanalization does not lead to complete tissue reperfusion in a considerable percentage of ischemic stroke patients. This study aimed to identify biomarkers associated with futile recanalization. Leukoaraiosis predicts poor outcomes of this phenomenon. Soluble tumour necrosis factor-like weak inducer of apoptosis (sTWEAK), which is associated with leukoaraiosis degrees, could be a potential biomarker. METHODS: This study includes two cohorts of ischemic stroke patients in a multicentre retrospective observational study. Effective reperfusion, defined as a reduction of ≥8 points in the National Institutes of Health Stroke Scale (NIHSS) within the first 24 h, was used as a clinical marker of effective reperfusion. RESULTS: In the first cohort study, female sex, age, and high NIHSS at admission (44.7% vs. 81.1%, 71.3 ± 13.7 vs. 81.1 ± 6.7; 16 [13, 21] vs. 23 [17, 28] respectively; p < .0001) were confirmed as predictors of futile recanalization. ROC curve analysis showed that leukocyte levels (sensitivity of 99%, specificity of 55%) and sTWEAK level (sensitivity of 92%, specificity of 88%) can discriminate between poor and good outcomes. Both biomarkers simultaneously are higher associated with outcome after effective reperfusion (OR: 2.17; CI 95% 1.63-4.19; p < .0001) than individually (leukocytes OR: 1.38; CI 95% 1.00-1.64, p = .042; sTWEAK OR: 1.00; C I95% 1.00-1.01, p = .019). These results were validated using a second cohort, where leukocytes and sTWEAK showed a sensitivity of 100% and specificity of 66.7% and 75% respectively. CONCLUSIONS: Leukocyte and sTWEAK could be biomarkers of reperfusion failure and subsequent poor outcomes. Further studies will be necessary to explore its role in reperfusion processes.

New Perspectives in Neuroprotection for Ischemic Stroke.

The constant failure of new neuroprotective therapies for ischemic stroke has partially halted the search for new therapies in recent years, mainly because of the high investment risk required to develop a new treatment for a complex pathology, such as stroke, with a narrow intervention window and associated comorbidities. However, owing to recent progress in understanding the stroke pathophysiology, improvement in patient care in stroke units, development of new imaging techniques, search for new biomarkers for early diagnosis, and increasingly widespread use of mechanical recanalization therapies, new opportunities have opened for the study of neuroprotection. This review summarizes the main protective agents currently in use, some of which are already in the clinical evaluation phase. It also includes an analysis of how recanalization therapies, new imaging techniques, and biomarkers have improved their efficacy.

Ionization, intrinsic basicity, and intrinsic acidity of unsaturated diols of astrochemical interest: 1,1- and 1,2-ethenediol: A theoretical survey.

The structure, stability, and bonding characteristics of 1,1- and 1,2-ethenediol, their radical cations, and their protonated and deprotonated species were investigated using high-level ab initio G4 calculations. The electron density of all the neutral and charged systems investigated was analyzed using the QTAIM, ELF, and NBO approaches. The vertical ionization potential (IP) of the five stable tautomers of 1,2-ethenediol and the two stable tautomers of 1,1-ethenediol go from 11.81 to 12.27 eV, whereas the adiabatic ones go from 11.00 to 11.72 eV. The adiabatic ionization leads to a significant charge delocalization along the O-C-C-O skeleton. The most stable protonated form of (Z)-1,2-ethenediol can be reached by the protonation of both the anti-anti and the syn-anti conformers, whereas the most stable deprotonated form arises only from the syn-anti one. Both charged species are extra-stabilized by the formation of an O-H···O intramolecular hydrogen bond (IHB) which is not found in the neutral system. (Z)-1,2-ethenediol is predicted to be less stable, less basic, and more acidic than its cis-glycolaldehyde isomer. The most stable protonated species of (E)-1,2-ethenediol comes from its syn-syn conformer, although the anti-anti conformer is the most basic one. Contrarily, the three conformers yield a common deprotonated species, so their acidity follows exactly their relative stability. Again, the (E)-1,2-ethenediol is predicted to be less stable, less basic, and more acidic than its trans-glycolaldehyde isomer. Neither the neutral nor the protonated or the deprotonated forms of 1,1-ethenediol show the formation of any O-H···O IHB. The most stable protonated species is formed by the protonation of any of the two tautomers, but the most stable deprotonated form arises exclusively from the syn-anti neutral conformer. The conformers of 1,1-ethenediol are much less stable and significantly less basic than their isomer, acetic acid, and only slightly more acidic.

A Holistic View of the Interactions between Electron-Deficient Systems: Clustering of Beryllium and Magnesium Hydrides and Halides.

In the search for common bonding patterns in pure and mixed clusters of beryllium and magnesium derivatives, the most stable dimers and trimers involving BeX2 and MgX2 (X = H, F, Cl) have been studied in the gas phase using B3LYP and M06-2X DFT methods and the G4 ab initio composite procedure. To obtain some insight into their structure, stability, and bonding characteristics, we have used two different energy decomposition formalisms, namely MBIE and LMO-EDA, in parallel with the analysis of the electron density with the help of QTAIM, ELF, NCIPLOT, and AdNDP approaches. Some interesting differences are already observed in the dimers, where the stability sequence observed for the hydrides differs entirely from that of the fluorides and chlorides. Trimers also show some peculiarities associated with the presence of compact trigonal cyclic structures that compete in stability with the more conventional hexagonal and linear forms. As observed for dimers, the stability of the trimers changes significantly from hydrides to fluorides or chlorides. Although some of these clusters were previously explored in the literature, the novelty of this work is to provide a holistic approach to the entire series of compounds by using chemical bonding tools, allowing us to understand the stability trends in detail and providing insights for a significant number of new, unexplored structures.

Association of periodontitis with cognitive decline and its progression: Contribution of blood-based biomarkers of Alzheimer's disease to this relationship.

AIM: To assess whether periodontitis is associated with cognitive decline and its progression as well as with certain blood-based markers of Alzheimer's disease. MATERIALS AND METHODS: Data from a 2-year follow-up prospective cohort study (n = 101) was analysed. Participants with a previous history of hypertension and aged ≥60 years were included in the analysis. All of them received a full-mouth periodontal examination and cognitive function assessments (Addenbrooke's Cognitive Examination (ACE) and Mini-Mental State Examination [MMSE]). Plasma levels of amyloid beta (Aß)1-40 , Aß1-42 , phosphorylated and total Tau (p-Tau and t-Tau) were determined at baseline, 12 and 24 months. RESULTS: Periodontitis was associated with poor cognitive performance (MMSE: ß = -1.5 [0.6]) and progression of cognitive impairment (hazard ratio [HR] = 1.8; 95% confidence interval: 1.0-3.1). Subjects with periodontitis showed greater baseline levels of p-Tau (1.6 [0.7] vs. 1.2 [0.2] pg/mL, p < .001) and Aß1-40 (242.1 [77.3] vs. 208.2 [73.8] pg/mL, p = .036) compared with those without periodontitis. Concentrations of the latter protein also increased over time only in the periodontitis group (p = .005). CONCLUSIONS: Periodontitis is associated with cognitive decline and its progression in elderly patients with a previous history of hypertension. Overexpression of p-Tau and Aß1-40 may play a role in this association.

Dispersion, Rehybridization, and Pentacoordination: Keys to Understand Clustering of Boron and Aluminum Hydrides and Halides.

The structure, stability, and bonding characteristics of dimers and trimers involving BX3 and AlX3 (X = H, F, Cl) in the gas phase, many of them explored for the first time, were investigated using different DFT (B3LYP, B3LYP/D3BJ, and M06-2X) and ab initio (MP2 and G4) methods together with different energy decomposition formalisms, namely, many-body interaction-energy and localized molecular orbital energy decomposition analysis. The electron density of the clusters investigated was analyzed with QTAIM, electron localization function, NCIPLOT, and adaptive natural density partitioning approaches. Our results for triel hydride dimers and Al2X6 (X = F, Cl) clusters are in good agreement with previous studies in the literature, but in contrast with the general accepted idea that B2F6 and B2Cl6 do not exist, we have found that they are predicted to be weakly bound systems if dispersion interactions are conveniently accounted for in the theoretical schemes used. Dispersion interactions are also dominant in both homo- and heterotrimers involving boron halide monomers. Surprisingly, B3F9 and B3Cl9 C3v cyclic trimers, in spite of exhibiting rather strong B-X (X = F, Cl) interactions, were found to be unstable with respect to the isolated monomers due to the high energetic cost of the rehybridization of the B atom, which is larger than the two- and three-body stabilization contributions when the cyclic is formed. Another important feature is the enhanced stability of both homo- and heterotrimers in which Al is the central atom because Al is systematically pentacoordinated, whereas this is not the case when the central atom is B, which is only tri- or tetra-coordinated.

Periodontitis is associated with subclinical cerebral and carotid atherosclerosis in hypertensive patients: A cross-sectional study.

OBJECTIVE: To examine the relationship between periodontitis and subclinical intracranial atherosclerosis. The association of periodontitis with preclinical markers of atherosclerosis in other vascular territories was also explored. MATERIAL AND METHODS: This was a cross-sectional study where 97 elderly subjects with a previous history of hypertension received an ultrasonographic evaluation to assess subclinical atherosclerosis in different vascular territories: (1) cerebral [pulsatility (PI) and resistance index (RI) of the middle cerebral artery], (2) carotid [intima-media thickness (IMT)], and (3) peripheral [ankle-brachial index (ABI)]. Additionally, participants underwent a full-mouth periodontal assessment together with blood sample collection to determine levels of inflammatory biomarkers (leukocytes, fibrinogen, and erythrocyte sedimentation rate), lipid fractions (total cholesterol and high- and low-density lipoprotein), and glucose. RESULTS: Sixty-one individuals had periodontitis. Compared to subjects without periodontitis, those with periodontitis showed higher values of PI (1.24 ± 0.29 vs 1.01 ± 0.16), RI (0.70 ± 0.14 vs 0.60 ± 0.06), and IMT (0.94 ± 0.15 vs 0.79 ± 0.15) (all p < 0.001). No statistically significant differences were found neither for ABI or for other clinical and biochemical parameters. An independent association was found between periodontitis and increased intracranial atherosclerosis (ORadjusted = 10.16; 95% CI: 3.14-32.90, p < 0.001) and to a lesser extent with thicker carotid IMT (ORadjusted = 4.10; 95% CI: 1.61-10.48, p = 0.003). CONCLUSIONS: Periodontitis is associated with subclinical atherosclerosis in both intracranial and carotid arteries in elderly subjects with hypertension. CLINICAL RELEVANCE: The association of periodontitis with intracranial atherosclerosis implies that periodontitis patients might have greater chances to develop ischemic stroke in the future.

Influence of Temperature Chronobiology on Stroke Outcome.

The circadian system regulates numerous physiological variables, including body temperature. Additionally, a circadian patter has been described in stroke onset. Considering this, we hypothesised that the chronobiology of temperature may have an impact on stroke onset and functional outcomes. We also studied the variation of blood biomarkers according to stroke onset time. This is a retrospective observational study. Of the patients included, 2763 had a stroke between midnight and 8:00 h; 1571 between 8:00-14:00 h; and 655 between 14:00 h and midnight. Axillary temperature was measured at admission. At this time, blood samples were collected for biomarker analysis (TNF-α, IL-1ß, IL-6, IL-10, and glutamate). Temperature was higher in patients admitted from 8:00 h to midnight (p < 0.0001). However, the percentage of poor outcome at 3 months was highest in patients from midnight to 8:00 h (57.7%, p < 0.001). The association between temperature and mortality was highest during night time (OR: 2.79; CI 95%: 2.36-3.28; p < 0.001). These patients exhibited high glutamate (220.2 ± 140.2 µM), IL-6 (32.8 ± 14.3 pg/mL) and low IL-10 (9.7 ± 14.3 pg/mL) levels. Therefore, temperature chronobiology could have a significant impact on stroke onset and functional outcome. Superficial body hyperthermia during sleep seems to be more dangerous than during wakefulness. Further studies will be necessary to confirm our data.

Resultados de un programa de ecocardioscopia realizada por neurólogos en el proceso integrado en red de atención al ictus en unidades de imagen cardiaca / Results of a focused cardiac ultrasound program conducted by neurologists within a stroke care network with cardiac imaging units

Introducción y objetivos Recientemente los neurólogos han comenzado a realizar ecocardioscopia para la detección de cardiopatías en pacientes con ictus isquémico, lo cual requiere un proceso previo de formación acreditada. Se diseñó un estudio prospectivo con el objetivo de analizar la incidencia de cardiopatías detectadas por ecocardioscopia en una unidad de ictus integrada en red con una Unidad de Imagen Cardiaca y el pronóstico de la detección de cardiopatía estructural a 1 año de seguimiento. Métodos Se incluyeron los casos que ingresaron por ictus isquémico o accidente isquémico transitorio en un hospital clínico universitario de 2017 a 2021 y fueron evaluados mediante ecocardioscopia. Se estudió la presencia de cardiopatía estructural y cardiopatía embolígena. Se analizaron los eventos cardiovasculares (ECV) durante el primer año de seguimiento. Resultados Se realizó ecocardioscopia a 706 pacientes. Se detectó cardiopatía estructural en el 52,1% de los casos y cardiopatía embolígena en el 31,9%. El 5,49% había sufrido ECV al año de seguimiento. La presencia de cardiopatía estructural de novo se asoció de manera independiente con una mayor probabilidad de ECV (HR=1,72; IC95%, 1,01-2,91; p=0,046). Conclusiones La ecocardioscopia dentro de un proceso integrado en red de atención al ictus con unidades de imagen cardiaca es una técnica accesible y de alta rentabilidad diagnóstica. Su uso permite actuaciones clínicas y terapéuticas directas en la prevención de nuevas embolias cerebrales y otros ECV en este grupo de pacientes. (AU)

Introduction and objectives Recently, neurologists have begun to perform focused cardiac ultrasound for the detection of a cardiac source of embolism in stroke patients, requiring them to undergo a prior accredited training process. We designed a prospective study to analyze the incidence of heart disease detected by a focused cardiac ultrasound program within a stroke care network with cardiac imaging units and to identify the outcomes of detected structural heart disease at 1 year of follow-up. Methods We included patients admitted to a university hospital for ischemic stroke or a transient ischemic attack between 2017 and 2021 who were evaluated by focused cardiac ultrasound. We studied the presence of structural heart disease and cardioembolic sources. We analyzed cardiovascular events (CVE) during the first year of follow-up. Results Focused cardiac ultrasound was performed in 706 patients. Structural heart disease was detected in 52.1% and a cardioembolic source in 31.9%. Adverse CVE occurred in 5.49% of the patients in the first year of follow-up. The presence of de novo structural heart disease was independently associated with a higher probability of adverse CVE (HR, 1.72; 95%CI, 1.01- 2.91; P=.046). Conclusions Focused cardiac ultrasound within a stroke care network with cardiac imaging units is an accessible technique with high diagnostic yield. Its use allows clinical and therapeutic actions in the prevention of stroke recurrences and other CVEs in this group of patients. (AU)

Results of a focused cardiac ultrasound program conducted by neurologists within a stroke care network with cardiac imaging units.

INTRODUCTION AND OBJECTIVES: Recently, neurologists have begun to perform focused cardiac ultrasound for the detection of a cardiac source of embolism in stroke patients, requiring them to undergo a prior accredited training process. We designed a prospective study to analyze the incidence of heart disease detected by a focused cardiac ultrasound program within a stroke care network with cardiac imaging units and to identify the outcomes of detected structural heart disease at 1 year of follow-up. METHODS: We included patients admitted to a university hospital for ischemic stroke or a transient ischemic attack between 2017 and 2021 who were evaluated by focused cardiac ultrasound. We studied the presence of structural heart disease and cardioembolic sources. We analyzed cardiovascular events (CVE) during the first year of follow-up. RESULTS: Focused cardiac ultrasound was performed in 706 patients. Structural heart disease was detected in 52.1% and a cardioembolic source in 31.9%. Adverse CVE occurred in 5.49% of the patients in the first year of follow-up. The presence of de novo structural heart disease was independently associated with a higher probability of adverse CVE (HR, 1.72; 95%CI, 1.01- 2.91; P=.046). CONCLUSIONS: Focused cardiac ultrasound within a stroke care network with cardiac imaging units is an accessible technique with high diagnostic yield. Its use allows clinical and therapeutic actions in the prevention of stroke recurrences and other CVEs in this group of patients.

Dismantlement of ammonia upon interaction with Ben (n ≤ 10) clusters.

The interaction of ammonia with Ben (n < 1-10) clusters has been investigated by density functional theory and ab initio calculations. The main conclusion is that, regardless of the size of the Be cluster, neither the structure of ammonia nor that of the Be clusters are preserved due to a systematic dissociation of its NH bonds and a spontaneous H-shift toward the available Be atoms. This H migration not only leads to rather stable BeH bonds, but dramatically enhances the strength of the BeN bonds as well. Accordingly, the maximum stability is found for the interaction with the beryllium trimer, leading to a complex with three NBe and three BeH bonds. Another maximum in stability, although lower than that reached for n = 3, is found for the Be heptamer, since from n = 6, a new NBe bond is formed, so that complexes from n = 6 to n = 10 are characterized by the formation of a NBe4 moiety, whose stability reaches a maximum at n = 7. The bonding characteristics of the different species formed are analyzed by means of AIM, NBO, ELF and AdNDP approaches.

20 Years of ICF-International Classification of Functioning, Disability and Health: Uses and Applications around the World.

The International Classification of Functioning Disability and Health (ICF) was approved in 2001 and, since then, several studies reported the increased interest about its use in different sectors. A recent overview that summarizes its applications is lacking. This study aims to provide an updated overview about 20 years of ICF application through an international online questionnaire, developed by the byline authors, and sent to each World Health Organization Collaborating Centers of the Family of International Classifications (WHO-FIC CCs). Data was collected during October 2020 and December 2021 and descriptive content analyses were used to report main results. Results show how, in most of the respondent countries represented by WHO-FIC CCs, ICF was mainly used in clinical practice, policy development and social policy, and in education areas. Despite its applications in different sectors, ICF use is not mandatory in most countries but, where used, it provides a biopsychosocial framework for policy development in health, functioning and disability. The study provides information about the needs related to ICF applications, that can be useful to organize targeted intervention plans. Furthermore, this survey methodology can be re-proposed periodically to monitor the use of the ICF in the future.

Open questions on toxic heavy metals Cd, Hg and Pb binding small components of DNA and nucleobases. Are there any predictable trends?

In this perspective article, we provide a bibliographic compilation of experimental and theoretical work on Cd, Hg, and Pb, and analyze in detail the bonding of M2+ and CH3M+ (M = Zn, Cd, Hg, Pb) with urea and thiourea as suitable models for larger biochemical bases. Through the use of DFT calculations, we have found that although in principle binding energies decrease according to ionic size (Zn2+ > Cd2+ > Pb2+), Hg2+ largely breaks the trend. Through the use of EDA (Energy Decomposition Analysis) it is possible to explain this behavior, which is essentially due to the strong contribution of polarization to the binding. This conclusion is ratified by the NEDA (Natural Energy Decomposition Analysis) formalism, showing that the charge transfer term is very large in all cases, but particularly in the case of the mercury-thiourea system. The general trends observed for the interactions with CH3M+ monocations show however CH3Hg+ binding energies systematically smaller than the CH3Zn+ ones, likely because the relativistic contraction of the Hg orbitals is very much attenuated by the attachment to the methyl group. Finally, we have investigated the gas-phase reactivity between EtHg+ and uracil to compare it with that exhibited by CH3Hg+ and n-ButHg+ previously described in the literature. This comparison gathers new information that highlights the importance of the length of the alkyl chain attached to the metal on the mechanisms of these reactions. For methyl mercury, only the alkyl transfer process is allowed; for butyl mercury, protonation is clearly favored, and for ethyl mercury, both paths are competitive experimentally.

Carotid web: the challenging diagnosis of an under-recognized entity.

BACKGROUND: Determining the cause of acute ischemic stroke is crucial for patient management, particularly for preventing future stroke. In recent years, carotid web (CW), a non-atherosclerotic disorder of the carotid wall, has been found to be an underestimated source of cerebral emboli. OBJECTIVE: The present study aimed to analyze the clinical, radiological, and pathological findings, along with the treatments performed in patients with CW and ipsilateral ischemic events. METHODS: Patients with anterior circulation ischemic stroke or transient ischemic attack and ipsilateral CW were prospectively included from January 2019 to December 2021. RESULTS: Nine patients were enrolled. The median age was 55 (43-62) years, with a female-to-male ratio of 3.5:1. Of the total, seven patients (78%) consulted for recurrent ipsilateral ischemic events. Despite medical treatment, 44% of the patients experienced new episodes. Computed tomographic angiography was suggestive of CW in all cases in which it was performed. The interval between the first ischemic event and diagnosis of CW was of 13 (6-68) months. After ruling out any other possible etiology, every patient underwent carotid revascularization, one underwent stenting and eight underwent carotidectomy. No severe or long-term complications were noted. Histological studies confirmed the diagnosis of CW. There were no recurrences after carotid revascularization during a follow-up of 24 (13-35) months. CONCLUSION: Knowledge of CW and differentiating it from atheroma plaques is essential, as medical management seems to be insufficient in many cases. Revascularization, which has been shown to be safe and effective, might be the best treatment modality.

Surrogate biomarkers of outcome for wake-up ischemic stroke.

BACKGROUND: Wake-up ischemic stroke (IS) has been usually excluded from acute stroke therapy options for being outside of the safe treatment window. We identified risk factors, and clinical or molecular biomarkers that could be therapeutic targets for wake-up stroke prevention, thus hopefully leading to a decrease in its mortality and disability in medium to long-term outcome. METHODS: 4251 ischemic stroke (IS) patients from a prospectively registered database were recruited; 3838 (90.3%) had known onset-symptom time, and 413 (9.7%) were wake-up strokes. The main endpoint was to analyze the association between different serum biomarkers with wake-up IS episodes and their progression. Leukocytes count, serum levels of C-reactive protein, fibrinogen, interleukin 6 (IL-6), and vitamin D were analyzed as inflammation biomarkers; N-terminal pro-B-type Natriuretic-Peptide and microalbuminuria, used as atrial/endothelial dysfunction biomarkers; finally, glutamate levels as excitotoxicity biomarker. In addition, demographic, clinical and neuroimaging variables associated with the time-evolution of wake-up IS patients and functional outcome at 3 months were evaluated. Good and poor functional outcome were defined as mRS ≤2 and mRS > 2 at 3 months, respectively. RESULTS: Wake-up IS showed a poorer outcome at 3-months than in patients with known on-set-symptom time (59.1% vs. 48.1%; p < 0.0001). Patients with wake-up IS had higher levels of inflammation biomarkers; IL-6 levels at admission (51.5 ± 15.1 vs. 27.8 ± 18.6 pg/ml; p < 0.0001), and low vitamin D levels at 24 h (5.6 ± 5.8 vs. 19.2 ± 9.4 ng/ml; p < 0.0001) are worthy of attention. In a logistic regression model adjusted for vitamin D, OR was 15.1; CI 95%: 8.6-26.3, p < 0.0001. However, we found no difference in vitamin D levels between patients with or without clinical-DWI mismatch (no: 18.95 ± 9.66; yes: 17.84 ± 11.77 ng/mL, p = 0.394). No difference in DWI volume at admission was found (49.3 ± 96.9 ml in wake-up IS patients vs. 51.7 ± 98.2 ml in awake IS patients; p = 0.895). CONCLUSIONS: Inflammatory biomarkers are the main factors that are strongly associated with wake-up IS episodes. Wake-up IS is associated with lower vitamin D levels. These data indicate that vitamin D deficiency could become a therapeutic target to reduce wake-up IS events.

Antihyperthermic Treatment in the Management of Malignant Infarction of the Middle Cerebral Artery.

Malignant infarction of the middle cerebral artery (m-MCA) is a complication of ischemic stroke. Since hyperthermia is a predictor of poor outcome, and antihyperthermic treatment is well tolerated, our main aim was to analyze whether the systemic temperature decrease within the first 24 h was associated with a better outcome. Furthermore, we studied potential biochemical and neuroimaging biomarkers. This is a retrospective observational analysis that included 119 patients. The temperature variations within the first 24 h were recorded. Biochemical laboratory parameters and neuroimaging variables were also analyzed. The temperature increase at the first 24 h (OR: 158.97; CI 95%: 7.29−3465.61; p < 0.001) was independently associated with a higher mortality. Moreover, antihyperthermic treatment (OR: 0.08; CI 95%: 0.02−0.38; p = 0.002) was significantly associated with a good outcome at 3 months. Importantly, antihyperthermic treatment was associated with higher survival at 3 months (78% vs. 50%, p = 0.003). Significant independently associations between the development of m-MCA and both microalbuminuria (OR: 1.01; CI 95%: 1.00−1.02; p = 0.005) and leukoaraiosis (OR: 3.07; CI 1.84−5.13−1.02; p < 0.0001) were observed. Thus, antihyperthermic treatment within the first 24 h was associated with both a better outcome and higher survival. An increased risk of developing m-MCA was associated with leukoaraiosis and an elevated level of microalbuminuria.

Disrupting bonding in azoles through beryllium bonds: Unexpected coordination patterns and acidity enhancement.

Although triazoles and tetrazole are amphoteric and may behave as weak acids, the latter property can be hugely enhanced by beryllium bonds. To explain this phenomenon, the structure and bonding characteristics of the complexes between triazoles and tetrazoles with one and two molecules of BeF2 have been investigated through the use of high-level G4 ab initio calculations. The formation of the complexes between the N basic sites of the azoles and the Be center of the BeF2 molecule and the (BeF2)2 dimer leads to a significant bonding perturbation of both interacting subunits. The main consequence of these electron density rearrangements is the above-mentioned increase in the intrinsic acidity of the azole subunit, evolving from a typical nitrogen base to a very strong nitrogenous acid. This effect is particularly dramatic when the interaction involves the (BeF2)2 dimer, that is, a Lewis acid much stronger than the monomer. Although the azoles investigated have neighboring N-basic sites, their interaction with the (BeF2)2 dimer yields a monodentate complex. However, the deprotonated species becomes extra-stabilized because a second N-Be bond is formed, leading to a new five-membered ring, with the result that the azole-(BeF2)2 complexes investigated become stronger nitrogenous acids than oxyacids such as perchloric acid.

The Smoking Paradox in Stroke Patients Under Reperfusion Treatment Is Associated With Endothelial Dysfunction.

Objective: This study aimed to explore the association between smoking habit and the serum levels of soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK), in relation with the functional outcome of patients with acute ischemic stroke undergoing reperfusion treatment. Methods: Observational and retrospective study of a series of patients with acute ischemic stroke subjected to reperfusion treatments. Clinical, analytical, and neuroimaging parameters were analyzed. The main endpoint was the functional outcome at 3 months, measured by the modified Ranking Scale (mRS). Logistic regression models were used to analyze the association between smoking and sTWEAK levels with functional outcome and leukoaraiosis. Results: The results showed that smoking habit was associated with a good functional outcome at 3 months in patients with stroke (OR: 3.52; 95% CI: 1.03-11.9; p = 0.044). However, this independent association was lost after adjusting by sTWEAK levels (OR 1.73; 95% CI: 0.86-13.28; p = 0.116). sTWEAK levels were significantly lower in smoker patients [4015.5 (973.66-7921.83) pg/ml vs. 5,628 (2,848-10,202) pg/ml, p < 0.0001], while sTWEAK levels were significantly higher in patients with poor functional outcomes at 3 months [10,284 (7,388-13.247) pg/ml vs. 3,405 (2,329-6,629) pg/ml, p < 0.0001]. Conclusion: The decrease in sTWEAK levels was associated with a good functional outcome in smoker patients with stroke undergoing reperfusion therapy.