Multicompartmental monitoring of legacy and currently used pesticides in a subtropical lake used as a drinking water source (Laguna del Cisne, Uruguay).

A pilot annual monitoring survey (April 2018-March 2019) was conducted to investigate the presence of pesticides in superficial water and fish in Laguna del Cisne, one of the most critical drinking water sources in Uruguay. A total of 25 pesticide residues were detected in superficial water (89.3 % of the samples). Pesticide's temporal distribution was associated with crops and livestock practices, with higher occurrences in spring and summer than in autumn and winter. The most frequent compounds in superficial water were the insecticide chlorantraniliprole, and the herbicides glyphosate (including its metabolite AMPA) and metolachlor. The levels of Organochlorine pesticide, p,p'-DDT, was in some cases two order of magnitude above the international water quality guidelines for Ambient Water Criteria. In fishes, eight different pesticides were detected, at concentrations from 1000 to 453,000 ng·kg-1. The most frequent pesticides found were propiconazole, chlorpyrifos, and p,p'-DDE. The widespread occurrence of pesticides in fish suggests potential exposure effects on fish populations and the aquatic ecosystem. The sampling approach of this work allowed monitoring the continuous concentrations of several pesticides in surface waters and fishes to establish the influence from past and current agriculture practices in Laguna del Cisne basin. For safety measures, continuous monitoring programs must be performed in this system to prevent toxicity impacts on aquatic organisms and human health.

Assessing care-related regret among nurses specialized in multiple sclerosis: A psychometric analysis of a new assessment battery.

Experiences of regret associated with caring for patients with multiple sclerosis (MS) can affect medical decisions. A non-interventional study was conducted to assess the dimensionality and item characteristics of a battery including the Regret Intensity Scale (RIS-10) and 15 items evaluating common situations experienced by nurses in MS care. A total of 97 nurses were included. The RIS-10 showed good internal reliability and a unidimensional structure according to Mokken analysis. All-item homogeneity coefficients exceeded 0.30, whereas scalability for the overall RIS-10 was 0.66, indicating a strong scale. This battery showed adequate psychometric properties to evaluate regret among MS nurses.

Influence of Cultivar on Nutritional Composition and Nutraceutical Potential of Pecan Growing in Uruguay.

Composition and antioxidant properties of sixteen pecan [Carya illinoinensis (Wangenh) K. Koch] cultivars grown simultaneously in a single experimental orchard in Uruguay were evaluated to characterize their nutritional properties and nutraceutical potential. The percentage of oil, moisture, ash, minerals, and proteins were determined and also the fatty acid profile. Total phenolic compounds [18-41 mg gallic acid equivalents (GAEs)/g], condensed tannin [2-12 mg catechin equivalents (CEs)/g], and tocopherols (110-163 µg/g) contents were estimated in nut kernels. Total phenolic compounds (32-117 mg GAE/g), condensed tannins (130-357 mg CE/g), and total anthocyanins (1-3 mg 3-glucoside cyanidin/g) were also determined for pecan shells. The antioxidant activity in shells [57.15-578.88 µmol Trolox equivalents (TEs)/g] was 5 times higher compared with the kernels (23.15-156.60 µmol TEs/g) measured with hydrophilic ORAC. Bioactive compounds concentrations present statistically significant genetic variability between cultivars studied (p < 0.05). The presence of phenolic compounds was related with high-antioxidant capacity in kernels and shells, and a strong correlation between content of total phenolic compounds and condensed tannins in pecan shells was found. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) show association between cultivars and the observed variables. The nutritional profile in the different cultivars showed the trends described in other countries, but this work shows some significant differences that could be attributed to the specific edaphoclimatic conditions of cultivation in Uruguay.

Preferences Toward Attributes of Disease-Modifying Therapies: The Role of Nurses in Multiple Sclerosis Care.

ABSTRACT: BACKGROUND: Nurses play an essential role in coordinating the care of patients with multiple sclerosis (MS) throughout their disease trajectory in a complex treatment landscape. The aim of this study was to assess nurses' preferences toward different disease-modifying therapy attributes. METHODS: We conducted a multicenter, noninterventional, cross-sectional study in collaboration with the Sociedad Española de Enfermería Neurológica. Nurses actively involved in MS care were invited to participate in the study. Prevention of disability progression, preservation of cognitive function, side effect profile and safety monitoring, and method of administration were the treatment attributes tested. Conjoint analysis was used to assess preferences in 8 simulated treatment options and rank them from most to least preferred. RESULTS: A total of 98 nurses were included in the study. The mean (SD) age was 44.7 (9.8) years, and 91.8% were female with a mean (SD) time of experience in MS care of 7.5 (5.4) years. Participants prioritized preservation of cognition (38.6%), followed by preventing disability progression (35.2%) and side effect risk and safety monitoring (13.5%). Route and frequency of administration were the least preferred attributes (7.4% and 5.3%, respectively). Estimated utilities were consistent across the sample according to sociodemographic and professional practice characteristics. CONCLUSIONS: Nurses' preferences toward treatments were mainly driven by efficacy attributes. This information may support the role of nurses in the multidisciplinary management of MS facilitating shared decision making.

Sick leave and occupational burnout among nurses caring for patients with multiple sclerosis.

BACKGROUND: Sick leave is a common problem among healthcare professionals. Nurses play a critical role in the multidisciplinary management of multiple sclerosis (MS). However, limited information is available on the phenomenon of sick leave among MS nurses. OBJECTIVE: The aim of this study was to assess the presence of sick leave among nurses caring for patients with MS and to identify associated factors. METHODS: We conducted a multicenter, non-interventional, cross-sectional, web-based study. Nurses involved in MS care from across Spain answered a survey composed of demographic characteristics, professional background, questions about their standard practice, and a behavioral battery including the Maslach Burnout Inventory - Human Services Survey (MBI-HSS). A multivariable logistic regression analysis was conducted to determine the association between nurses' characteristics and sick leave. RESULTS: Ninety-six nurses were included in the study. Mean age (SD) was 44.6 (9.8) years, and 91.7% were female. Participants had a median of 6 (IQR 3.0, 11.0) years of expertise in MS managing a median of 15 (5.0, 35.0) patients per week. Sixteen participants (16.7%) had been on sick leave in the last 6 months, with a median absence of 14.5 days (7.0, 30.0). Sixteen nurses (16.7%) reported severe burnout. Participants on sick leave had higher levels of emotional exhaustion (mean MBI-HSS scores of 22.3 and 16.0, p=0.01) and inadequate interactions with their colleagues (mean Practice Environment Scale - Nursing Work Index scores of 11.8 and 13.1, p=0.01) than their counterparts. Burnout was associated with higher risk of sick leave in the multivariable analysis (OR=1.06 [95% CI 1.00, 1.13], p=0.04) after adjustment for confounders. CONCLUSIONS: Occupational burnout is associated with increased risk of sick leave among nurses managing patients with MS. Identifying burnout may be critical for implementing specific intervention strategies to maintain an adequate functioning of MS care units.

Behavioral aspects of nurse practitioners associated with optimal multiple sclerosis care in Spain.

BACKGROUND: Nurse practitioners (NPs) play a critical role in the multidisciplinary management of patients with multiple sclerosis (MS). Neurologists´ behavioral characteristics have been associated with suboptimal clinical decisions. However, limited information is available on their impact among NPs involved in MS care. The aim of this study was to assess nurses´ therapeutic choices to understand behavioral factors influencing their decision making process. METHODS: A non-interventional, cross-sectional, web-based study was conducted. NPs actively involved in the care of patients with MS were invited to participate in the study by the Spanish Society of Neurology Nursing. Participants answered questions regarding their standard practice and therapeutic management of seven simulated relapsing-remitting MS (RRMS) case scenarios. A behavioral battery was used to measure participants´ life satisfaction, mood, positive social behaviors, feeling of helpfulness, attitudes toward adoption of evidence-based innovations, occupational burnout, and healthcare-related regret. The outcome of interest was therapeutic inertia (TI), defined as the lack of treatment escalation when there is clinical and radiological evidence of disease activity. A score to quantify TI was created based on the number of simulated scenarios where treatment intensification was warranted. RESULTS: Overall, 331 NPs were invited to participate, 130 initiated the study, and 96 (29%) completed the study. The mean age (SD) was 44.6 (9.8) years and 91.7% were female. Seventy-three participants (76.0%) felt their opinions had a significant influence on neurologists´ therapeutic decisions. Sixteen NPs (16.5%) showed severe emotional exhaustion related to work and 13 (13.5%) had depressive symptoms. The mean (SD) TI score was 0.97 (1.1). Fifty-six of NPs showed TI in at least one case scenario. Higher years of nursing experience (p = 0.014), feeling of helpfulness (p = 0.014), positive attitudes toward innovations (p = 0.046), and a higher intensity of care-related regret (p = 0.021) were associated with a lower risk of TI (adjusted R2 = 0.28). Burnout was associated with higher risk of TI (p = 0.001). CONCLUSIONS: Although NPs cannot prescribe MS treatments in Spain, their behavioral characteristics may influence the management of patients with RRMS. Continuing education and specific strategies for reducing occupational burnout may lead to better management skills and improve MS care.

Antenatal diagnosis of jejunal atresia by 3D HDlive ultrasound: Case report and literature review / Diagnóstico prenatal de atresia de yeyuno con ecografía 3D con reconstrucción en superficie (HDlive): reporte de caso y revisión de la literatura

Objectives: To report the case of a patient with a prenatal diagnosis of jejunal atresia and to review the literature regarding the results and prenatal diagnosis of this entity, implementing the use of non-conventional methods (3D ultrasound or magnetic resonance imaging). Material and methods: Report of a case of an 18-year-old pregnant woman referred to the Maternal-Fetal Medicine, Genetics and Reproduction Unit of the Virgen del Rocío Hospital in Seville due to fetus with abdominal peristaltic cystic image, consistent with jejunal atresia, confirmed with 3D HDLive mode ultrasound. A bibliographic search was carried out in Medline/PubMed, Google Scholar and LILACS, restricting by type of language (English and Spanish) and date of publication (January 1995 to June 2020). Primary studies of reports and case series relating to the outcome and prenatal diagnosis of this pathology were included. Results: The search identified 1,033 titles, of which four studies met the inclusion criteria, these being reports or case series. A total of twelve fetuses with a prenatal diagnosis of jejunal atresia detected with unconventional methods were reported. In all cases, the prenatal diagnosis was confirmed during the neonatal period, which required resection of the compromised segment; one of them died and two neonates developed short bowel syndrome because of a wide bowel resection. The postoperative course in the remaining cases was favorable. Conclusion: The available literature on the prenatal diagnosis of jejunal atresia using non-conventional methods is scarce and is limited to case reports or case series. The literature reviewed suggests that, in the presence of intestinal dilation, 3D ultrasound and magnetic resonance imaging could be of some use in characterizing the atretic portion and establishing the differential diagnosis. More studies are required to evaluate the diagnostic utility of these two alternatives.

Objetivos: reportar el caso de una paciente con diagnóstico prenatal de atresia de yeyuno y hacer una revisión de la literatura en torno al resultado y al diagnóstico de esta entidad, implementando el uso de métodos no convencionales: ecografía tridimensional (3D) o resonancia magnética fetal (RM). Materiales y métodos: se reporta el caso de una gestante de 18 años, remitida a la Unidad de Medicina Materno-Fetal, Genética y Reproducción del Hospital Virgen del Rocío de Sevilla (España), por feto con imagen quística abdominal, peristáltica, compatible con atresia de yeyuno, la cual se confirmó con ecografía 3D modo HDlive. Se realizó una búsqueda bibliográfica en Medline/PubMed, LILACS y Google Scholar, restringiendo por tipo de idioma (inglés y español) y fecha de publicación (enero de 1995 a junio de 2020). Se incluyeron estudios primarios de reportes y series de caso, que abordaran el resultado y el diagnóstico prenatal de esta patología. Resultados: la búsqueda identificó 1.033 títulos, de los cuales cuatro estudios cumplieron con los criterios de inclusión, estos fueron reporte o series de casos. En total se reportaron doce fetos con diagnóstico prenatal de atresia de yeyuno detectada con métodos no convencionales. Una gestación finalizó con óbito a la semana 26 de gestación y en todos los demás casos, el diagnóstico se ratificó durante el periodo neonatal, requiriendo la resección del segmento comprometido. Dos neonatos desarrollaron síndrome de intestino corto como consecuencia de una resección intestinal amplia. El resto experimentó una evolución posoperatoria favorable. Conclusión: la literatura disponible en torno al diagnóstico prenatal de atresia de yeyuno utilizando métodos no convencionales es escasa y se limita a reporte o series de casos. La literatura revisada sugiere que, en presencia de dilatación intestinal, la ecografía 3D y la resonancia magnética fetal podrían tener cierta utilidad a la hora de caracterizar la porción atrésica y establecer el diagnóstico diferencial. Se requieren más estudios que evalúen la utilidad diagnóstica de estas dos alternativas.

Regret and Therapeutic Decisions in Multiple Sclerosis Care: Literature Review and Research Protocol.

Background: Decisions based on erroneous assessments may result in unrealistic patient and family expectations, suboptimal advice, incorrect treatment, or costly medical errors. Regret is a common emotion in daily life that involves counterfactual thinking when considering alternative choices. Limited information is available on care-related regret affecting healthcare professionals managing patients with multiple sclerosis (MS). Methods: We reviewed identified gaps in the literature by searching for the combination of the following keywords in Pubmed: "regret and decision," "regret and physicians," and "regret and nurses." An expert panel of neurologists, a nurse, a psychiatrist, a pharmacist, and a psychometrics specialist participated in the study design. Care-related regret will be assessed by a behavioral battery including the standardized questionnaire Regret Intensity Scale (RIS-10) and 15 new specific items. Six items will evaluate regret in the most common social domains affecting individuals (financial, driving, sports-recreation, work, own health, and confidence in people). Another nine items will explore past and recent regret experiences in common situations experienced by healthcare professionals caring for patients with MS. We will also assess concomitant behavioral characteristics of healthcare professionals that could be associated with regret: coping strategies, life satisfaction, mood, positive social behaviors, occupational burnout, and tolerance to uncertainty. Planned Outcomes: This is the first comprehensive and standardized protocol to assess care-related regret and associated behavioral factors among healthcare professionals managing MS. These results will allow to understand and ameliorate regret in healthcare professionals. Spanish National Register (SL42129-20/598-E).

Diagnóstico prenatal de atresia de yeyuno con ecografía 3D con reconstrucción en superficie (HDlive): reporte de caso y revisión de la literatura / Antenatal diagnosis of jejunal atresia by 3D HDlive ultrasound: Case report and literature review

Resumen Objetivos: Reportar el caso de una paciente con diagnóstico prenatal de atresia de yeyuno y hacer una revisión de la literatura en torno al resultado y al diagnóstico de esta entidad, implementando el uso de métodos no convencionales: ecografía tridimensional (3D) o resonancia magnética fetal (RM). Materiales y métodos: Se reporta el caso de una gestante de 18 años, remitida a la Unidad de Medicina Materno-Fetal, Genética y Reproducción del Hospital Virgen del Rocío de Sevilla (España), por feto con imagen quística abdominal, peristáltica, compatible con atresia de yeyuno, la cual se confirmó con ecografía 3D modo HDlive. Se realizó una búsqueda bibliográfica en Medline/PubMed, LILACS y Google Scholar, restringiendo por tipo de idioma (inglés y español) y fecha de publicación (enero de 1995 a junio de 2020). Se incluyeron estudios primarios de reportes y series de caso, que abordaran el resultado y el diagnóstico prenatal de esta patología. Resultados: La búsqueda identificó 1.033 títulos, de los cuales cuatro estudios cumplieron con los criterios de inclusión, estos fueron reporte o series de casos. En total se reportaron doce fetos con diagnóstico prenatal de atresia de yeyuno detectada con métodos no convencionales. Una gestación finalizó con óbito a la semana 26 de gestación y en todos los demás casos, el diagnóstico se ratificó durante el periodo neonatal, requiriendo la resección del segmento comprometido. Dos neonatos desarrollaron síndrome de intestino corto como consecuencia de una resección intestinal amplia. El resto experimentó una evolución posoperatoria favorable. Conclusión: La literatura disponible en torno al diagnóstico prenatal de atresia de yeyuno utilizando métodos no convencionales es escasa y se limita a reporte o series de casos. La literatura revisada sugiere que, en presencia de dilatación intestinal, la ecografía 3D y la resonancia magnética fetal podrían tener cierta utilidad a la hora de caracterizar la porción atrésica y establecer el diagnóstico diferencial. Se requieren más estudios que evalúen la utilidad diagnóstica de estas dos alternativas.

Abstract Objectives: To report the case of a patient with a prenatal diagnosis of jejunal atresia and to review the literature regarding the results and prenatal diagnosis of this entity, implementing the use of non-conventional methods (3D ultrasound or magnetic resonance imaging). Material and methods: Report of a case of an 18-year-old pregnant woman referred to the Maternal-Fetal Medicine, Genetics and Reproduction Unit of the Virgen del Rocío Hospital in Seville due to fetus with abdominal peristaltic cystic image, consistent with jejunal atresia, confirmed with 3D HDLive mode ultrasound. A bibliographic search was carried out in Medline/PubMed, Google Scholar and LILACS, restricting by type of language (English and Spanish) and date of publication (January 1995 to June 2020). Primary studies of reports and case series relating to the outcome and prenatal diagnosis of this pathology were included. Results: The search identified 1,033 titles, of which four studies met the inclusion criteria, these being reports or case series. A total of twelve fetuses with a prenatal diagnosis of jejunal atresia detected with unconventional methods were reported. In all cases, the prenatal diagnosis was confirmed during the neonatal period, which required resection of the compromised segment; one of them died and two neonates developed short bowel syndrome because of a wide bowel resection. The postoperative course in the remaining cases was favorable. Conclusion: The available literature on the prenatal diagnosis of jejunal atresia using non-conventional methods is scarce and is limited to case reports or case series. The literature reviewed suggests that, in the presence of intestinal dilation, 3D ultrasound and magnetic resonance imaging could be of some use in characterizing the atretic portion and establishing the differential diagnosis. More studies are required to evaluate the diagnostic utility of these two alternatives.

N370S-GBA1 mutation causes lysosomal cholesterol accumulation in Parkinson's disease.

BACKGROUND: Heterozygous mutations in the GBA1 gene, which encodes the lysosomal enzyme ß-glucocerebrosidase-1, increase the risk of developing Parkinson's disease, although the underlying mechanisms remain unclear. The aim of this study was to explore the impact of the N370S-GBA1 mutation on cellular homeostasis and vulnerability in a patient-specific cellular model of PD. METHODS: We isolated fibroblasts from 4 PD patients carrying the N370S/wild type GBA1 mutation and 6 controls to study the autophagy-lysosome pathway, endoplasmic reticulum stress, and Golgi apparatus structure by Western blot, immunofluorescence, LysoTracker and Filipin stainings, mRNA analysis, and electron microscopy. We evaluated cell vulnerability by apoptosis, reactive oxygen species and mitochondrial membrane potential with flow cytometry. RESULTS: The N370S mutation produced a significant reduction in ß-glucocerebrosidase-1 protein and enzyme activity and ß-glucocerebrosidase-1 retention within the endoplasmic reticulum, which interrupted its traffic to the lysosome. This led to endoplasmic reticulum stress activation and triggered unfolded protein response and Golgi apparatus fragmentation. Furthermore, these alterations resulted in autophagosome and p62/SQSTM1 accumulation. This impaired autophagy was a result of dysfunctional lysosomes, indicated by multilamellar body accumulation probably caused by increased cholesterol, enlarged lysosomal mass, and reduced enzyme activity. This phenotype impaired the removal of damaged mitochondria and reactive oxygen species production and enhanced cell death. CONCLUSIONS: Our results support a connection between the loss of ß-glucocerebrosidase-1 function, cholesterol accumulation, and the disruption of cellular homeostasis in GBA1-PD. Our work reveals new insights into the cellular pathways underlying PD pathogenesis, providing evidence that GBA1-PD shares common features with lipid-storage diseases. © 2017 International Parkinson and Movement Disorder Society.

Medicinal Plant Diversity and Inter-Cultural Interactions between Indigenous Guarani, Criollos and Polish Migrants in the Subtropics of Argentina.

Numerous studies highlight the importance of phytotherapy for indigenous and non-indigenous people in different parts of the world. In this work we analyze the richness (number of species), diversity (plant identity and the number of illnesses for which it is used) and similarity of plant species and illnesses treated with them, in order to contribute new data and insight into the importance of plant medicines to the local medical systems of people living in Misiones province, in the subtropics of Argentina. Three sympatric groups were compared: Guarani Indians, Criollos (mestizos) and Polish migrants. Quantitative scrutiny was focused on both primary and secondary sources. The similarity and diversity of medicinal plants and uses between groups was calculated by applying the Sørensen quantitative coefficient and the Shannon-Wiener index, respectively. In order to identify the characteristic plant species used by each group, the Cultural Importance and Prevalence Value (CIPV) was calculated based on the species Indicator Value (IndVal), which combines a species relative abundance with its relative frequency of occurrence in the various groups, and modified according to the type of the analyzed data. The important finding is a great variation in the number of species used by the study groups. Altogether, 509 botanical species were registered: Guarani (397), Criollos (243) and Polish migrants (137). For all groups, the use of native medicinal plants prevailed. The Guarani appear to be the local experts in use of medicinal plants. There is the significant difference in the number of treated illnesses by each taxon among three groups. Criollos and Polish migrants exhibit the greatest similarity in illnesses treated with medicinal plants. These groups share a corpus of knowledge related to illness nosology, and have a symptomatic approach to illness treatment. The Guarani have an etiological approach to illness diagnosis and healing, which may be viewed as a barrier to the exchange of knowledge about home medicine with other ethnic groups of Misiones.

Pectinase production by Aspergillus giganteus in solid-state fermentation: optimization, scale-up, biochemical characterization and its application in olive-oil extraction.

The application of pectinases in industrial olive-oil processes is restricted by its production cost. Consequently, new fungal strains able to produce higher pectinase titers are required. The aim of this work was to study the capability of Aspergillus giganteus NRRL10 to produce pectinolytic enzymes by SSF and evaluate the application of these in olive-oil extraction. A. giganteus was selected among 12 strains on the basis of high pectinolytic activity and stability. A mixture composed by wheat bran, orange, and lemon peels was selected as the best substrate for enzyme production. Statistical analyses of the experimental design indicated that pH, temperature, and CaCl2 are the main factors that affect the production. Subsequently, different aeration flows were tested in a tray reactor; the highest activity was achieved at 20 L min-1 per kilogram of dry substrate (kgds). Finally, the pectinolytic enzymes from A. giganteus improved the oil yield and rheological characteristics without affecting oil chemical properties.

Straightforward and robust synthesis of monodisperse surface-functionalized gold nanoclusters.

Gold nanoclusters are small (1-3 nm) nanoparticles with a high surface area that are useful for biomedical studies and drug delivery. The synthesis of small, surface-functionalized gold nanoclusters is greatly dependent on the reaction conditions. Here, we describe a straightforward, efficient and robust room temperature one-pot synthesis of 2 nm gold nanoclusters using thioglucose as a reducing and stabilizing agent, which was discovered by serendipity. The resultant monodisperse gold nanoclusters are more stable than those generated using some other common methods. The carboxylic acid contained in the stabilizing agent on the cluster surface serves as anchor for nanocluster functionalization. Alternatively, the addition of thiols serves to functionalize the nanoclusters. The resulting non-cytotoxic nanoclusters are taken up by cells and constitute a tuneable platform for biomedical applications including drug delivery.

Fullerenols and glucosamine fullerenes reduce infarct volume and cerebral inflammation after ischemic stroke in normotensive and hypertensive rats.

Cerebral inflammation plays a crucial role in the pathophysiology of ischemic stroke and is involved in all stages of the ischemic cascade. Fullerene derivatives, such as fullerenol (OH-F) are radical scavengers acting as neuroprotective agents while glucosamine (GlcN) attenuates cerebral inflammation after stroke. We created novel glucosamine-fullerene conjugates (GlcN-F) to combine their protective effects and compared them to OH-F regarding stroke-induced cerebral inflammation and cellular damage. Fullerene derivatives or vehicle was administered intravenously in normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) immediately after transient middle cerebral artery occlusion (tMCAO). Infarct size was determined at day 5 and neurological outcome at days 1 and 5 after tMCAO. CD68- and NeuN-staining were performed to determine immunoreactivity and neuronal survival respectively. Cytokine and toll like receptor 4 (TLR-4) expression was assessed using quantitative real-time PCR. Magnetic resonance imaging revealed a significant reduction of infarct volume in both, WKY and SHR that were treated with fullerene derivatives. Treated rats showed an amelioration of neurological symptoms as both OH-F and GlcN-F prevented neuronal loss in the perilesional area. Cerebral immunoreactivity was reduced in treated WKY and SHR. Expression of IL-1ß and TLR-4 was attenuated in OH-F-treated WKY rats. In conclusion, OH-F and GlcN-F lead to a reduction of cellular damage and inflammation after stroke, rendering these compounds attractive therapeutics for stroke.

Carbohydrate functionalization of silver nanoparticles modulates cytotoxicity and cellular uptake.

BACKGROUND: Increasing use of silver nanoparticles (Ag-NPs) in various products is resulting in a greater likelihood of human exposure to these materials. Nevertheless, little is still known about the influence of carbohydrates on the toxicity and cellular uptake of nanoparticles. METHODS: Ag-NPs functionalized with three different monosaccharides and ethylene glycol were synthesized and characterised. Oxidative stress and toxicity was evaluated by protein carbonylation and MTT assay, respectively. Cellular uptake was evaluated by confocal microscopy and ICP-MS. RESULTS: Ag-NPs coated with galactose and mannose were considerably less toxic to neuronal-like cells and hepatocytes compared to particles functionalized by glucose, ethylene glycol or citrate. Toxicity correlated to oxidative stress but not to cellular uptake. CONCLUSIONS: Carbohydrate coating on silver nanoparticles modulates both oxidative stress and cellular uptake, but mainly the first has an impact on toxicity. These findings provide new perspectives on modulating the bioactivity of Ag-NPs by using carbohydrates.

Imaging early endothelial inflammation following stroke by core shell silica superparamagnetic glyconanoparticles that target selectin.

Activation of the endothelium is a pivotal first step for leukocyte migration into the diseased brain. Consequently, imaging this activation process is highly desirable. We synthesized carbohydrate-functionalized magnetic nanoparticles that bind specifically to the endothelial transmembrane inflammatory proteins E and P selectin. Magnetic resonance imaging revealed that the targeted nanoparticles accumulated in the brain vasculature following acute administration into a clinically relevant animal model of stroke, though increases in selectin expression were observed in both brain hemispheres. Nonfunctionalized naked particles also appear to be a plausible agent to target the ischemic vasculature. The importance of these findings is discussed regarding the potential for translation into the clinic.

On the role of surface composition and curvature on biointerface formation and colloidal stability of nanoparticles in a protein-rich model system.

The need for a better understanding of nanoparticle-protein interactions and the mechanisms governing the resulting colloidal stability has been emphasised in recent years. In the present contribution, the short and long term colloidal stability of silica nanoparticles (SNPs) and silica-poly(ethylene glycol) nanohybrids (Sil-PEG) have been scrutinised in a protein model system. Well-defined silica nanoparticles are rapidly covered by bovine serum albumin (BSA) and form small clusters after 20min while large agglomerates are detected after 10h depending on both particle size and nanoparticle-protein ratio. Oppositely, Sil-PEG hybrids present suppressive protein adsorption and enhanced short and long term colloidal stability in protein solution. No critical agglomeration was found for either system in the absence of protein, proving that instability found for SNPs must arise as a consequence of protein adsorption and not to high ionic environment. Analysis of the small angle X-ray scattering (SAXS) structure factor indicates a short-range attractive potential between particles in the silica-BSA system, which is in good agreement with a protein bridging agglomeration mechanism. The results presented here point out the importance of the nanoparticle surface properties on the ability to adsorb proteins and how the induced or depressed adsorption may potentially drive the resulting colloidal stability.