A heteronuclear ZnGd complex as a potential contrast agent for magnetic resonance imaging

The 20th International Electronic Conference on Synthetic Organic Chemistry session Bioorganic, Medicinal and Natural ProductsA new ligand H3L, with internal compartments for allocating 3d metal ions and external donors to bind 4f ions, was synthesized and completely characterized. Reaction of H3L with zinc(II) and gadolin ium(III) salts allows isolating the heteronuclear complex {[ZnGd(HL)(NO3)(OAc)(CH3OH)](NO3)}∙6H2O (1·6H2O). The ability of 1·6H2O to act as a magnetic resonance imaging (MRI) contrast agent was evaluated and this study shows that both the transversal and longitudinal relaxivities are quite high but the T1/T2 ratio of 7.9 indicates that it could have even greater potential as a T2 contrast agen

Is PRP useful in alveolar cleft reconstruction? Platelet-rich plasma in secondary alveoloplasty

Objective: Cleft lip and palate is a congenital facial malformation with an established treatment protocol. Mixed dentition period is the best moment for correct maxillary bone defect with an alveoloplasty. The aim of this surgical procedure is to facilitate dental eruption, re-establish maxillary arch, close any oro-nasal communication, give support to nasal ala, and in some cases allow dental rehabilitation with osteointegrated implants. Study design: Twenty cleft patients who underwent secondary alveoloplasty were included. In 10 of them autogenous bone graft were used and in other 10 autogenous bone and platelet-rich plasma (PRP) obtained from autogenous blood. Bone formation was compared by digital orthopantomography made on immediate post-operatory and 3 and 6 months after the surgery. Results: No significant differences were found between both therapeutic groups on bone regeneration. Conclusion: We do not find justified the use of PRP for alveoloplasty in cleft patients? treatment protocol

Intraarterial route increases the risk of cerebral lesions after mesenchymal cell administration in animal model of ischemia

Mesenchymal stem cells (MSCs) are a promising clinical therapy for ischemic stroke. However, critical parameters, such as the most effective administration route, remain unclear. Intravenous (i.v.) and intraarterial (i.a.) delivery routes have yielded varied outcomes across studies, potentially due to the unknown MSCs distribution. We investigated whether MSCs reached the brain following i.a. or i.v. administration after transient cerebral ischemia in rats, and evaluated the therapeutic effects of both routes. MSCs were labeled with dextran-coated superparamagnetic nanoparticles for magnetic resonance imaging (MRI) cell tracking, transmission electron microscopy and immunohistological analysis. MSCs were found in the brain following i.a. but not i.v. administration. However, the i.a. route increased the risk of cerebral lesions and did not improve functional recovery. The i.v. delivery is safe but MCS do not reach the brain tissue, implying that treatment benefits observed for this route are not attributable to brain MCS engrafting after stroke.This study has been partially supported by grants from Axencia Galega de Innovación (Xunta de Galicia), the Instituto de Salud Carlos III (PI13/00292; PI14/01879), the Spanish Research Network on Cerebrovascular Diseases RETICS-INVICTUS (RD12/0014), Xunta de Galicia (Consellería Educación GRC2014/027), the European Commission program FEDER and Promoting Active Ageing program: Functional Nanostructures For Alzheimer’s Disease At Ultra-Early Stages” (Pana_686009), a Research and Innovation Project, funded within the EU Horizon 2020 Programme”. Furthermore, this study was also co-funded within the POCTEP (Operational Programme for Cross-border Cooperation Spain-Portugal) program (0681_INVENNTA_1_E), co-financed by the ERDF (European Regional Development Fund). T. Sobrino (CP12/03121) and F. Campos (CP14/00154) are recipients of a research contract from Miguel Servet Program of Instituto de Salud Carlos III. Finally, P. Taboada thanks Mineco and Xunta de Galicia for funding through projects MAT2013-40971-R and EM2013-046, respectively. J Trekker is the recipient of an innovation grant from the IWT-VlaanderenS

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 futureOpen Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This study was partially supported by grants from the Xunta de Galicia (TS: IN607A2018/3 and TS: IN607D 2020/09), Spanish Ministry of Science (TS: RTI2018-102165-B-I00 and RTC2019-007373-1), Institute of Health Carlos III (PI22/00938), and RICOR-ICTUS Network (RD21/0006/003). Furthermore, this study was also supported by grants from the Interreg Atlantic Area (TS: EAPA_791/2018_ NeuroATLANTIC project), Interreg V-A España Portugal (POCTEP) (TS: 0624_2IQBIONEURO_6_E), and the European Regional Development Fund. YL is supported by a Sara Borrell fellowship (CD22/00051), and TS (CPII17/00027) and FC (CPII19/00020) are recipients of Miguel Servet contracts, all of them funded by the Institute of Health Carlos IIIS

Random Forest-Based Prediction of Stroke Outcome

[Abstract] We research into the clinical, biochemical and neuroimaging factors associated with the outcome of stroke patients to generate a predictive model using machine learning techniques for prediction of mortality and morbidity 3-months after admission. The dataset consisted of patients with ischemic stroke (IS) and non-traumatic intracerebral hemorrhage (ICH) admitted to Stroke Unit of a European Tertiary Hospital prospectively registered. We identified the main variables for machine learning Random Forest (RF), generating a predictive model that can estimate patient mortality/morbidity according to the following groups: (1) IS + ICH, (2) IS, and (3) ICH. A total of 6022 patients were included: 4922 (mean age 71.9 ± 13.8 years) with IS and 1100 (mean age 73.3 ± 13.1 years) with ICH. NIHSS at 24, 48 h and axillary temperature at admission were the most important variables to consider for evolution of patients at 3-months. IS + ICH group was the most stable for mortality prediction [0.904 ± 0.025 of area under the receiver operating characteristics curve (AUC)]. IS group presented similar results, although variability between experiments was slightly higher (0.909 ± 0.032 of AUC). ICH group was the one in which RF had more problems to make adequate predictions (0.9837 vs. 0.7104 of AUC). There were no major differences between IS and IS + ICH groups according to morbidity prediction (0.738 and 0.755 of AUC) but, after checking normality with a Shapiro Wilk test with the null hypothesis that the data follow a normal distribution, it was rejected with W = 0.93546 (p-value < 2.2e−16). Conditions required for a parametric test do not hold, and we performed a paired Wilcoxon Test assuming the null hypothesis that all the groups have the same performance. The null hypothesis was rejected with a value < 2.2e−16, so there are statistical differences between IS and ICH groups. In conclusion, machine learning algorithms RF can be effectively used in stroke patients for long-term outcome prediction of mortality and morbidity.This study was partially supported by grants from the Spanish Ministry of Science and Innovation (SAF2017-84267-R), Xunta de Galicia (Axencia Galega de Innovación (GAIN): IN607A2018/3), Instituto de Salud Carlos III (ISCIII) (PI17/00540, PI17/01103), Spanish Research Network on Cerebrovascular Diseases RETICS-INVICTUS PLUS (RD16/0019) and by the European Union FEDER program. T. Sobrino (CPII17/00027), F. Campos (CPII19/00020) are recipients of research contracts from the Miguel Servet Program (Instituto de Salud Carlos III). General Directorate of Culture, Education and University Management of Xunta de Galicia (ED431G/01,252 ED431D 2017/16), “Galician Network for Colorectal Cancer Research" (Ref. ED431D 2017/23), Competitive Reference Groups (ED431C 2018/49), Spanish Ministry of Economy and Competitiveness via funding of the unique installation BIOCAI (UNLC08-1E-002, UNLC13-13–3503), European Regional Development Funds (FEDER).Xunta de Galicia; IN607A2018/3Xunta de Galicia; ED431G/01,252Xunta de Galicia; ED431D 2017/1

Temperature-Induced Changes in Reperfused Stroke: Inflammatory and Thrombolytic Biomarkers

Although hyperthermia is associated with poor outcomes in ischaemic stroke (IS), some studies indicate that high body temperature may benefit reperfusion therapies. We assessed the association of temperature with effective reperfusion (defined as a reduction of ≥8 points in the National Institute of Health Stroke Scale (NIHSS) within the first 24 h) and poor outcome (modified Rankin Scale (mRS) > 2) in 875 retrospectively-included IS patients. We also studied the influence of temperature on thrombolytic (cellular fibronectin (cFn); matrix metalloproteinase 9 (MMP-9)) and inflammatory biomarkers (tumour necrosis factor-alpha (TNF-α), interleukin 6 (IL-6)) and their relationship with effective reperfusion. Our results showed that a higher temperature at 24 but not 6 h after stroke was associated with failed reperfusion (OR: 0.373, p = 0.001), poor outcome (OR: 2.190, p = 0.005) and higher IL-6 levels (OR: 0.958, p 37.5 °C at 24 h, but not at 6 h after stroke, is correlated with reperfusion failure, poor clinical outcome, and infarct size. Mild hyperthermia (36.5–37.5 °C) in the first 6 h window might benefit drug reperfusion therapies by promoting clot lysisThis study was partially supported by grants from the Spanish Ministry of Science and Innovation (SAF2017-84267-R), Xunta de Galicia (Consellería Educación: IN607A2018/3), Instituto de Salud Carlos III (ISCIII) (PI17/00540 and PI17/01103), Spanish Research Network on Cerebrovascular Diseases RETICS-INVICTUS PLUS (RD16/0019), and by the European Union FEDER program. Furthermore, Tomás. Sobrino (CPII17/00027) and Francisco Campos (CPII19/00020) are recipients of research contracts from the Miguel Servet Program of Instituto de Salud Carlos III. María Pérez-Mato is a Sara Borrell Researcher (CD19/00033)S

Association of High Serum Levels of Growth Factors with Good Outcome in Ischemic Stroke : a Multicenter Study

Altres ajuts: This project was partially supported by grants from Xunta de Galicia (Consellería Educación: GRC2014/027 and IN607A2018/3), Spanish Research Network on Cerebrovascular Diseases RETICS-INVICTUS PLUS (RD16/0019), and by the European Union FEDER program.The main objective of this research work was to study the association of serum levels of growth factors (GF) and SDF-1α with the functional outcome and reduction of lesion volume in ischemic stroke patients. In this multicenter study, 552 patients with non-lacunar stroke (male, 62.1%; mean age, 68.2 ± 11.4) were included within 24 h from symptom onset. The main outcome variable was good functional outcome (modified Rankin Scale [mRS] ≤ 2) at 12 months. Secondary outcome variable was infarct volume (in mL) after 6 ± 3 months. Serum levels of VEGF, Ang-1, G-CSF, BDNF, and SDF-1α were measured by ELISA at admission, 7 ± 1 days, at 3 ± 1 months, and 12 ± 3 months. Except for BDNF, all GF and SDF-1α serum levels showed a peak value at day 7 and remained elevated during the first 3 months (all p < 0.01). High serum levels at day 7 of VEGF (OR, 19.3), Ang-1 (OR, 14.7), G-CSF (OR, 9.6), and SDF-1α (OR, 28.5) were independently associated with good outcome at 12 months (all p < 0.0001). On the other hand, serum levels of VEGF (B, − 21.4), G-CSF (B, − 14.0), Ang-1 (B, − 13.3), and SDF-1α (B, − 44.6) measured at day 7 were independently associated with lesion volume at 6 months (p < 0.01). In summary, high serum levels of VEGF, Ang-1, G-CSF, and SDF-1α at day 7 and 3 months after ischemic stroke are associated with good functional outcome and smaller residual lesion at 1 year of follow-up

Soil and Freshwater Bioassays to Assess Ecotoxicological Impact on Soils Affected by Mining Activities in the Iberian Pyrite Belt

This study aims to use geochemical, mineralogical, ecotoxicological and biological indicators for a comprehensive assessment of the ecological risks related to the mobility, ecotoxicity and bioavailability of potentially harmful elements in the Lousal mining district. Particularly, toxicity was evaluated using four assays: algae, cytotoxicity assays with HaCaT cell line (dermal), earthworms and Daphnia magna. The geochemical and mineralogical characterization of the studied area shows that the mine wastes underwent intense weathering processes, producing important contamination of the adjacent soils, which also led to the release and mobilization of PHEs into nearby water courses. Total PTE results indicate that the soils affected by mining activities were highly contaminated with As and Cu, while Zn and Pb content ranged from low to very high, depending on the analyzed samples. Cadmium levels were found to be very low in most of the soil samples. The test using Daphnia magna was the most sensitive bioassay, while the Eisenia foetida test was the least sensitive. Except for the LOS07 soil sample, the rest of the soils were classified as “High acute toxicity” and “Very high acute toxicity” for aquatic systems. The results in HACaT cells showed results similar to the ecotoxicological bioassays. The application of biotests, together with geochemical and mineralogical characterization, is a very useful tool to establish the degree of contamination and the environmental risk of potentially harmful elements

Evaluación del riesgo ecotoxicológico en suelos afectados por actividades mineras en la Faja Pirítica mediante aplicación de bioensayos

Depto. de Geodinámica, Estratigrafía y PaleontologíaDepto. de Mineralogía y PetrologíaFac. de Ciencias GeológicasTRUEMinisterio de Ciencia e Innovación (MICINN) MCIN AEI/10.13039/501100011033pu

Influence of Sex on Stroke Prognosis: A Demographic, Clinical, and Molecular Analysis

Identifying the complexities of the effect of sex on stroke risk, etiology, and lesion progression may lead to advances in the treatment and care of ischemic stroke (IS) and non-traumatic intracerebral hemorrhage patients (ICH). We studied the sex-related discrepancies on the clinical course of patients with IS and ICH, and we also evaluated possible molecular mechanisms involved. The study's main variable was the patient's functional outcome at 3-months. Logistic regression models were used in order to study the influence of sex on different inflammatory, endothelial and atrial dysfunction markers. We recruited 5,021 patients; 4,060 IS (54.8% male, 45.2% female) and 961 ICH (57.1% male, 42.9% female). Women were on average 5.7 years older than men (6.4 years in IS, 5.1 years in ICH), and more likely to have previous poor functional status, to suffer atrial fibrillation and to be on anticoagulants. IS patients showed sex-related differences at 3-months regarding poorer outcome (55.6% women, 43.6% men, p &lt; 0.0001), but this relationship was not found in ICH (56.8% vs. 61.9%, p = 0.127). In IS, women had higher levels of NT-proBNP and 3-months worse outcome in both cardioembolic and non-cardioembolic stroke patients. Stroke patients showed sex-related differences in pre-hospital data, clinical variables and molecular markers, but only IS patients presented independent sex-related differences in 3-months poor outcome and mortality. There was a relationship between the molecular marker of atrial dysfunction NT-proBNP and worse functional outcome in women, resulting in a possible indicator of increased dysfunction