Perampanel as adjuvant treatment in epileptic encephalopathies: A multicenter study in routine clinical practice.

OBJECTIVE: Developmental and epileptic encephalopathies (DEEs) are a heterogeneous group of syndromes, including Lennox-Gastaut syndrome (LGS), which are refractory to multiple therapies. Perampanel efficacy has been reported in LGS but further real-world evidence is needed in DEEs. METHODS: A multicenter, retrospective, 1-year observational study in patients with DEEs on adjuvant perampanel treatment was conducted to assess perampanel safety and effectiveness in this type of patients in a real-world setting. Seizure types [focal onset seizures (FOS), generalized tonic-clonic seizures (GTCS), tonic seizures (TS), atonic seizures (AtS), atypical absences (AA), and myoclonic seizures (MS)] and seizure clusters were divided in different frequency groups: daily, weekly, and monthly seizures, and absent or seizure freedom. Patients could have more than one seizure type. For each frequency group, group change and seizure freedom were analyzed. RESULTS: Eighty-seven patients diagnosed with DEEs (45 males) of median age 22 [1-70] years were included. The most frequent DEEs were LGS (35.6%) and Lennox-like syndrome (37.9%). At baseline 20 patients had three to five types of seizures, 36 patients had two types of seizures and 31 patients had one predominant type of seizure. The mean number of seizure types per patient at baseline was 2.12 ± 0.97 which was reduced to 1.62 ± 0.91 at 12 months (p < 0.001). Overall, 51.7% of patients had a significant improvement in at least one seizure type. At baseline, 45 patients had GTCS, 42 FOS, 41 TS, 18 AA, 16 AtS, 11 MS, and 30 seizures clusters. Seizure freedom for each specific type at 12 months was significantly achieved by 35% of patients with GTCS (p < 0.001), 17% (p = 0.016) with TS and 37% with seizure clusters (p < 0.001). Patients achieved seizure freedom from other seizure types but with no statistical significance: 7% FOS-free, 28% AA-free, 6% Ats-free, and 18% MS-free. Regarding changes of group at 12 months, 22% of TS and 19% of FOS improved significantly to a group with lower seizure frequency (p = 0.004 and p = 0.02, respectively). In remaining groups (4% of GTCS, 11% of AA, 18% of Ats, 18% of MS, and 13% of seizure clusters), the improvement was not statistically significant. Twenty-nine patients discontinued perampanel: 18 (21%) due to AEs, 8 (9%) due to lack of efficacy, and 3 (3%) due to seizure worsening. Adverse events, mostly mild or moderate, were reported in 53% of patients, and irritability/mood changes (22%) and somnolence (17%) were the most frequent. CONCLUSION: This is the first large-scale real-world study with perampanel across different seizure types in patients with DEEs. Perampanel was effective, especially in GTCS, TS, and FOS, as well as in seizure clusters. Perampanel was generally well-tolerated without unexpected AEs.

Effectiveness and safety of perampanel monotherapy for focal and generalized tonic-clonic seizures: Experience from a national multicenter registry.

OBJECTIVE: To assess the effectiveness and tolerability of perampanel (PER) monotherapy in routine clinical practice for the treatment of focal onset and generalized tonic-clonic seizures (GTCS). METHODS: This multicenter, retrospective, observational study was conducted in patients aged ≥12 years treated with PER as primary monotherapy or converted to PER monotherapy by progressive reduction of background antiepileptic drugs. Outcomes included retention, responder, and seizure-free rate after 3, 6, and 12 months and tolerability throughout the follow-up. RESULTS: A total of 98 patients (mean age = 49.6 ± 21.7 years, 51% female) with focal seizures and/or GTCS were treated with PER monotherapy for a median exposure of 14 months (range = 1-57) with a median dose of 4 mg (range = 2-10). The retention rates at 3, 6, and 12 months and last follow-up were 93.8%, 89.3%, 80.9%, and 71.4%, respectively. The retention rates according to the type of monotherapy (primary vs conversion) did not differ (log-rank P value = .57). Among the 98 patients, 61.2% patients had seizures throughout the baseline period, with a median seizure frequency of 0.6 seizures per month (range = 0.3-26). Responder rates at 3, 6, and 12 months were 79.6%, 70.1%, and 52.8%, respectively, and seizure freedom rates at the same points were 62.7%, 56.1%, and 41.5%. Regarding the 33 patients who had GTCS in the baseline period, 87.8% were seizure-free at 3 months, 78.1% at 6 months, and 55.1% at 12 months. Over the entire follow-up, PER monotherapy was generally well tolerated, and only 16% of patients discontinued PER due to adverse events (AEs). Female patients were found to be at a higher risk of psychiatric AEs (female vs male odds ratio = 2.85, 95% confidence interval = 1-8.33, P = .046). SIGNIFICANCE: PER demonstrated good effectiveness and a good safety profile when used as primary therapy or conversion to monotherapy at relatively low doses, in a clinical setting with patients with focal seizures and GTCS.

Areas for improvement in community optometry: flashes and floaters take priority.

PURPOSE: A common response to rising demand for healthcare is to extend the role of health professionals and the range of their service provision. Community optometry in Scotland is a recent example of this. Within this context of innovation and change there are challenges to ensuring quality in optometry practice. The purpose of this research is to establish what the priorities are for practice improvement within community optometry and to start a programme to inform strategies to improve practice. METHODS: A four stage study was conducted: (1) a service-driven topic prioritisation exercise to identify priorities for optometry practice improvement; (2) a review of national and international guidance and UK protocols relating to the identified priority topic; (3) a national theory-based survey identifying current practice and the barriers and facilitators to the target behaviour; and (4) the identification of theory-based intervention options to improve practice. The Behaviour Change Wheel approach to behaviour change intervention development and Theoretical Domains Framework (TDF) provided the underlying theoretical framework. RESULTS: Stakeholders identified 'patients presenting with flashes and floaters' as an important priority for practice improvement. The decision about whether or not to refer patients on to secondary care for further examination is the target behaviour. Guidance for optometrists on this topic is lacking. Six TDF domains were related to the decision about whether or not to refer patients with flashes and floaters to secondary care - 'social influences', 'emotion', 'beliefs about capabilities', 'beliefs about consequences', 'behavioural regulation' and 'reinforcement'. CONCLUSIONS: This study has examined current practice in relation to the management of patients with flashes and floaters, identified the most salient targets for future strategies to improve optometry practice and highlighted what form these strategies may take. It demonstrates the use of a flexible, theory-informed approach, which can be used to engage with stakeholders and professionals to inform the design and development of efforts to improve practice in a variety of healthcare settings.

Efficacy and safety of eslicarbazepine acetate monotherapy for partial-onset seizures: Experience from a multicenter, observational study.

Eslicarbazepine acetate (ESL, Aptiom™) is a once-daily anticonvulsant, approved as adjunctive treatment of partial-onset seizures (POS). Historical-controlled trials investigating the use of ESL as monotherapy have demonstrated a favorable efficacy and tolerability profile in patients with POS. This prospective, non-interventional study recruited POS patients in 17 hospitals in Spain. After a 3-month baseline period, ESL therapy was initiated as 400mg QD and up-titrated to an optimal maintenance dose based on clinical response and tolerance. The incidence of seizures was assessed via seizure calendars and the nature and severity of adverse events (AEs) were also recorded. A total of 117 patients (aged 9-87years) enrolled in the study and were treated with ESL at either 400mg/day (3.4% patients), 800mg/day (61% patients), 1200mg/day (27.1% patients) or 1600mg/day (8.5% patients). At 3months, 82.0% (n=72) of patients achieved a ≥50% reduction in seizure frequency, compared to 79.7% (n=67) of patients at 6months and 83.0% (n=49) at 12months. Patients who suffered secondary generalized tonic-clonic (SGTC) seizures had seizure-free rates of 71% (n=27), 69.6% (n=29), and 72.7% (n=16) at 3, 6, and 12months, respectively. Overall, 18 patients (15.3%) reported AEs of instability and dizziness (n=9), somnolence (n=3), mild hyponatremia (n=3), headache (n=1), hypertriglyceridemia (n=1), and allergic reaction (n=1), which caused ESL discontinuation of ESL treatment. ESL is effective and well tolerated as monotherapy for patients with POS, which supports previous findings. Early use is supported by its frequent use as monotherapy in this study and lack of severe side effects.

Clinical stakeholders' opinions on the use of selective decontamination of the digestive tract in critically ill patients in intensive care units: an international Delphi study.

INTRODUCTION: Selective decontamination of the digestive tract (SDD) is a prophylactic antibiotic regimen that is not widely used in practice. We aimed to describe the opinions of key 'stakeholders' about the validity of the existing evidence base, likely consequences of implementation, relative importance of their opinions in influencing overall practice, likely barriers to implementation and perceptions of the requirement for further research to inform the decision about whether to embark on a further large randomised controlled trial. METHODS: This was a Delphi study informed by comprehensive framework of possible determinants of health professionals' behaviour to study Critical Care practice in four countries. There were four key stakeholder participant groups including ICU physicians, pharmacists, clinical leads, and clinical microbiologists/ infectious disease physicians. Round one comprised participant interviews and Rounds two and three were online questionnaires using Delphi method. RESULTS: In this study, 141 participants were recruited of whom 82% were retained. Participants rated themselves as knowledgeable about SDD. Antibiotic resistance was identified as the most important issue. SDD was seen as a low clinical priority but few participants reported strong opposition. There was moderate agreement that research to date has not adequately addressed concerns about antibiotic resistance and lacks generalizability. Participants indicated equipoise with regard to benefits and harms of SDD, and indicated strong support for a further randomised trial. CONCLUSIONS: Clinicians have clinical equipoise about the effectiveness of SDD. Future research requires longer follow up to assess antibiotic resistance as well as greater validity/generalizability to provide definitive answers on the effectiveness of decontamination and effects on antibiotic resistance. SDD was regarded as not being a high clinical priority, which may limit future trial participation. These results have identified that further large randomised controlled trial of SDD in critical care is both warranted and appropriate.

Theoretical and empirical dimensions of the Aberdeen Glaucoma Questionnaire: a cross sectional survey and principal component analysis.

BACKGROUND: To develop patient-reported outcome instruments, statistical techniques (e.g., principal components analysis; PCA) are used to examine correlations among items and identify interrelated item subsets (empirical factors). However, interpretation and labelling of empirical factors is a subjective process, lacking precision or conceptual basis. We report a novel and reproducible method for mapping between theoretical and empirical factor structures. We illustrate the method using the pilot Aberdeen Glaucoma Questionnaire (AGQ), a new measure of glaucoma-related disability developed using the International Classification of Functioning and Disability (ICF) as a theoretical framework and tested in a sample representing the spectrum of glaucoma severity. METHODS: We used the ICF to code AGQ item content before mailing the AGQ to a UK sample (N = 1349) selected to represent people with a risk factor for glaucoma and people with glaucoma across a range of severity. Reflecting uncertainty in the theoretical framework (items with multiple ICF codes), an exploratory PCA was conducted. The theoretical structure informed our interpretation of the empirical structure and guided the selection of theoretically-derived factor labels. We also explored the discrimination of the AGQ across glaucoma severity groups. RESULTS: 656 (49%) completed questionnaires were returned. The data yielded a 7-factor solution with a simple structure (using cut-off point of a loading of 0.5) that together accounted for 63% of variance in the scores. The mapping process resulted in allocation of the following theoretically-derived factor labels: 1) Seeing Functions: Participation; 2) Moving Around & Communication; 3) Emotional Functions; 4) Walking Around Obstacles; 5) Light; 6) Seeing Functions: Domestic & Social Life; 7) Mobility. Using the seven factor scores as independent variables in a discriminant function analysis, the AGQ scores resulted in correct glaucoma severity grading of 32.5% of participants (p < 0.001). CONCLUSIONS: This paper addresses a methodological gap in the application of classical test theory (CTT) techniques, such as PCA, in instrument development. Labels for empirically-derived factors are often selected intuitively whereas they can inform existing bodies of knowledge if selected on the basis of theoretical construct labels, which are more explicitly defined and which relate to each other in ways that are evidence based.

Clinical components and associated behavioural aspects of a complex healthcare intervention: multi-methods study of selective decontamination of the digestive tract in critical care.

BACKGROUND: This study sought to identify and describe the clinical and behavioural components (e.g. the what, how, when, where and by whom) of 'selective decontamination of the digestive tract' (SDD) as routinely implemented in the care of critically ill patients. METHODS: Multi-methods study, consisting of semi-structured observations of SDD delivery, interviews with clinicians and documentary analysis, conducted in two ICUs in the UK that routinely deliver SDD. Data were analysed within-site to describe clinical and behavioural SDD components and synthesised across-sites to describe SDD in context. RESULTS: SDD delivery involved multiple behaviours extending beyond administration of its clinical components. Not all behaviours were specified in relevant clinical documentation. Overall, SDD implementation and delivery included: adoption (i.e. whether to implement SDD), operationalisation (i.e. implementing SDD into practice), provision (i.e. delivery of SDD) and surveillance (i.e. monitoring the ecological effects). Implementation involved organisational, team and individual-level behaviours. Delivery was perceived as easy by individual staff, but displayed features of complexity (including multiple interrelated behaviours, staff and contexts). CONCLUSIONS: This study is the first to formally outline the full spectrum of clinical and behavioural aspects of SDD. It identified points in the delivery process where complex behaviours occur and outlined how SDD can be interpreted and applied variably in practice. This comprehensive specification allows greater understanding of how this intervention could be implemented in units not currently using it, or replicated in research studies. It also identified strategies required to adopt SDD and to standardise its implementation.

Using Metal-Organic Framework HKUST-1 for the Preparation of High-Conductive Hybrid Membranes Based on Multiblock Copolymers for Fuel Cells.

Novel proton-conducting hybrid membranes consisting of sulfonated multiblock copolymer of polysulfone and polyphenylsulfone (SPES) reinforced with a HKUST-1 metal-organic framework (MOF) (5, 10, and 20 wt. %) were prepared and characterized for fuel cell applications. The presence of the MOF in the copolymer was confirmed by means of FE-SEM and EDS. The hybrid membranes show a lower contact angle value than the pure SPES, in agreement with the water uptake (WU%), i.e., by adding 5 wt. % of the MOF, this parameter increases by 20% and 40% at 30 °C and 60 °C, respectively. Additionally, the presence of the MOF increases the ion exchange capacity (IEC) from 1.62 to 1.93 mequivH+ g−1. Thermogravimetric analysis reveals that the hybrid membranes demonstrate high thermal stability in the fuel cell operation temperature range (<100 °C). The addition of the MOF maintains the mechanical stability of the membranes (TS > 85 MPa in the Na+ form). Proton conductivity was analyzed using EIS, achieving the highest value with a 5 wt. % load of the HKUST-1. This value is lower than that observed for the HKUST-1/Nafion system. However, polarization and power density curves show a remarkably better performance of the hybrid membranes in comparison to both the pure SPES and the pure Nafion membranes.

The Effect of the Extra Virgin Olive Oil Minor Phenolic Compound 3',4'-Dihydroxyphenylglycol in Experimental Diabetic Kidney Disease.

The aim of this study was to analyze the possible nephroprotective effect of 3',4'-dihydroxyphenylglycol (DHPG), a polyphenolic compound of extra virgin olive oil (EVOO), on renal lesions in an experimental model of type 1 diabetes. Rats were distributed as follows: healthy normoglycemic rats (NDR), diabetic rats treated with saline (DR), and DR treated with 0.5 mg/kg/day or 1 mg/kg/day of DHPG. DR showed a significantly higher serum and renal oxidative and nitrosative stress profile than NDR, as well as reduced prostacyclin production and renal damage (defined as urinary protein excretion, reduced creatinine clearance, increased glomerular volume, and increased glomerulosclerosis index). DHPG reduced the oxidative and nitrosative stress and increased prostacyclin production (a 59.2% reduction in DR and 34.7-7.8% reduction in DHPG-treated rats), as well as 38-56% reduction in urinary protein excretion and 22-46% reduction in glomerular morphological parameters (after the treatment with 0.5 or 1 mg/kg/day, respectively). Conclusions: DHPG administration to type 1-like diabetic rats exerts a nephroprotective effect probably due to the sum of its antioxidant (Pearson's coefficient 0.68-0.74), antinitrosative (Pearson's coefficient 0.83), and prostacyclin production regulator (Pearson's coefficient 0.75) effects.

Modeling the antimicrobial effects of olive mill waste extract, rich in hydroxytyrosol, on the growth of lactic acid bacteria using response surface methodology.

The objective of this study is to assess the inhibitory effects of an aqueous extract from olive oil mill waste (alperujo) on the growth of a lactic acid bacteria (LAB) cocktail consisting of various strains of Lactiplantibacillus pentosus and Lactiplantibacillus plantarum species. For this purpose, response surface methodology was employed using two independent variables (pH levels 3.5-5.55; hydroxytyrosol concentration ranging from 0.93-2990 ppm). The response variable was the average inhibition per treatment on the LAB cocktail (expressed as a percentage). The developed model identified significant terms, including the linear effect of hydroxytyrosol and pH, their interaction, and the quadratic effect of pH. Maximum inhibition of the LAB cocktail was observed at progressively higher concentrations of hydroxytyrosol and lower pH values. Therefore, complete inhibition of LAB in the synthetic culture medium could only be achieved for concentrations of 2984 ppm hydroxytyrosol at a pH of 3.95. These findings suggest that extracts derived from "alperujo" could be utilized as a natural preservative in acidified foods with a bitter flavor and antioxidant requirements.

Characterization and Modeling of Free Volume and Ionic Conduction in Multiblock Copolymer Proton Exchange Membranes.

Free volume plays a key role on transport in proton exchange membranes (PEMs), including ionic conduction, species permeation, and diffusion. Positron annihilation lifetime spectroscopy and electrochemical impedance spectroscopy are used to characterize the pore size distribution and ionic conductivity of synthesized PEMs from polysulfone/polyphenylsulfone multiblock copolymers with different degrees of sulfonation (SPES). The experimental data are combined with a bundle-of-tubes model at the cluster-network scale to examine water uptake and proton conduction. The results show that the free pore size changes little with temperature in agreement with the good thermo-mechanical properties of SPES. However, the free volume is significantly lower than that of Nafion®, leading to lower ionic conductivity. This is explained by the reduction of the bulk space available for proton transfer where the activation free energy is lower, as well as an increase in the tortuosity of the ionic network.

Neuroprotective Effect of 3',4'-Dihydroxyphenylglycol in Type-1-like Diabetic Rats-Influence of the Hydroxytyrosol/3',4'-dihydroxyphenylglycol Ratio.

The aim of this study was to assess the possible neuroprotective effect of 3',4'-dihydroxyphenylglycol (DHPG), a polyphenol from extra virgin olive oil (EVOO), in an experimental model of diabetes and whether this effect is modified by the presence of another EVOO polyphenol, hydroxytyrosol (HT). The neuroprotective effect was assessed in a hypoxia-reoxygenation model in brain slices and by quantifying retinal nerve cells. The animals were distributed as follows: (1) normoglycemic rats (NDR), (2) diabetic rats (DR), (3) DR treated with HT (5 mg/kg/day p.o.), (4) DR treated with DHPG (0.5 mg/kg/day), or (5) with 1 mg/kg/day, (6) DR treated with HT plus DHPG 0.5 mg/kg/day, or (7) HT plus 1 mg/kg/day p.o. DHPG. Diabetic animals presented higher levels of oxidative stress variables and lower numbers of neuronal cells in retinal tissue. The administration of DHPG or HT reduced most of the oxidative stress variables and brain lactate dehydrogenase efflux (LDH) as an indirect index of cellular death and also reduced the loss of retinal cells. The association of DHPG+HT in the same proportions, as found in EVOO, improved the neuroprotective and antioxidant effects of both polyphenols.

Pre-validation methods for developing a patient reported outcome instrument.

BACKGROUND: Measures that reflect patients' assessment of their health are of increasing importance as outcome measures in randomised controlled trials. The methodological approach used in the pre-validation development of new instruments (item generation, item reduction and question formatting) should be robust and transparent. The totality of the content of existing PRO instruments for a specific condition provides a valuable resource (pool of items) that can be utilised to develop new instruments. Such 'top down' approaches are common, but the explicit pre-validation methods are often poorly reported. This paper presents a systematic and generalisable 5-step pre-validation PRO instrument methodology. METHODS: The method is illustrated using the example of the Aberdeen Glaucoma Questionnaire (AGQ). The five steps are: 1) Generation of a pool of items; 2) Item de-duplication (three phases); 3) Item reduction (two phases); 4) Assessment of the remaining items' content coverage against a pre-existing theoretical framework appropriate to the objectives of the instrument and the target population (e.g. ICF); and 5) qualitative exploration of the target populations' views of the new instrument and the items it contains. RESULTS: The AGQ 'item pool' contained 725 items. Three de-duplication phases resulted in reduction of 91, 225 and 48 items respectively. The item reduction phases discarded 70 items and 208 items respectively. The draft AGQ contained 83 items with good content coverage. The qualitative exploration ('think aloud' study) resulted in removal of a further 15 items and refinement to the wording of others. The resultant draft AGQ contained 68 items. CONCLUSIONS: This study presents a novel methodology for developing a PRO instrument, based on three sources: literature reporting what is important to patient; theoretically coherent framework; and patients' experience of completing the instrument. By systematically accounting for all items dropped after the item generation phase, our method ensures that the AGQ is developed in a transparent, replicable manner and is fit for validation. We recommend this method to enhance the likelihood that new PRO instruments will be appropriate to the research context in which they are used, acceptable to research participants and likely to generate valid data.

Choosing appropriate patient-reported outcomes instrument for glaucoma research: a systematic review of vision instruments.

PURPOSE: To identify vision Patient-Reported Outcomes instruments relevant to glaucoma and assess their content validity. METHODS: MEDLINE, MEDLINE in Process, EMBASE and SCOPUS (to January 2009) were systematically searched. Observational studies or randomised controlled trials, published in English, reporting use of vision instruments in glaucoma studies involving adults were included. In addition, reference lists were scanned to identify additional studies describing development and/or validation to ascertain the final version of the instruments. Instruments' content was then mapped onto a theoretical framework, the World Health Organization International Classification of Functioning, Disability and Health. Two reviewers independently evaluated studies for inclusion and quality assessed instrument content. RESULTS: Thirty-three instruments were identified. Instruments were categorised into thirteen vision status, two vision disability, one vision satisfaction, five glaucoma status, one glaucoma medication related to health status, five glaucoma medication side effects and six glaucoma medication satisfaction measures according to each instruments' content. The National Eye Institute Visual Function Questionnaire-25, Impact of Vision Impairment and Treatment Satisfaction Survey-Intraocular Pressure had the highest number of positive ratings in the content validity assessment. CONCLUSION: This study provides a descriptive catalogue of vision-specific PRO instruments, to inform the choice of an appropriate measure of patient-reported outcomes in a glaucoma context.

Synthesis and Characterization of Novel Anion Exchange Membranes Based on Semi-Interpenetrating Networks of Functionalized Polysulfone: Effect of Ionic Crosslinking.

In this work, anion exchange membranes based on polymer semi-interpenetrating networks were synthesized and characterized for the first time. The networks are composed of sulfonated polysulfone and 1-methylimidazolium-functionalized polysulfone crosslinked covalently with N,N,N',N'-tetramethylethylenediamine (degree of crosslinking of 5%). In these membranes, sulfonic groups interact electrostatically with cationic groups to form an ionic crosslinking structure with improved alkaline stability. The effect of the ionic crosslinking on the thermal, chemical, mechanical, and electrochemical behavior of membranes was studied. These crosslinked membranes containing sulfonated polysulfone showed higher thermal stability, with a delay of around 20 °C in the onset decomposition temperature value of the functional groups than the crosslinked membranes containing free polysulfone. The tensile strength values were maintained above 44 MPa in all membranes with a degree of chloromethylation (DC) below 100%. The maximum ionic conductivity value is reached with the membrane with the highest degree of chloromethylation. The chemical stability in alkaline medium of the conducting membranes also improved. Thus, the ionic conductivity variation of the membranes after 96 h in a 1 M potassium hydroxide (KOH) solution is less pronounced when polysulfone is replaced by sulfonated polysulfone. So, the ionic crosslinking which joins both components of the blends together, improves the material's properties making progress in the development of new solid electrolyte for polymeric fuel cells.

Antioxidant Capacity and Phenolic and Sugar Profiles of Date Fruits Extracts from Six Different Algerian Cultivars as Influenced by Ripening Stages and Extraction Systems.

The study investigated the phenols, sugar and the antioxidant capacities of date fruit extracts obtained by organic solvents and by hydrothermal treatment from six different Algerian cultivars at two ripening stages for the first time. The analyzed cultivars exhibited potent antioxidant properties (ferric reducing antioxidant power (FRAP), 1,1-Diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) scavenging capacities) and different phenols regardless of the solvents and the maturity stages. About 18 phenols were identified and quantified, mainly in the hydrothermal extracts. The earlier stages were characterized by high amounts of o-coumaric acid, cinnamic acid and luteolin, with a noticeable absence of quercetin. The tamr stage presented the highest sugar content (78.15-86.85 mg/100 mg dry weight (DW)) with an abundance of glucose. Galactose was present only in some cultivars from the kimri stage (tamjouhert). Uronic acids were mostly detected at the tamr stage (4.02-8.82 mg gallic acid equivalent/100 mg dried weight). The obtained results highlight the potential of using date fruit extracts as natural antioxidants, especially at industrial scales that tend use hydrothermal extraction.

Sulfonated Polysulfone/TiO2(B) Nanowires Composite Membranes as Polymer Electrolytes in Fuel Cells.

New proton conducting membranes based on sulfonated polysulfone (sPSU) reinforced with TiO2(B) nanowires (1, 2, 5 and 10 wt.%) were synthesized and characterized. TiO2(B) nanowires were synthesized by means of a hydrothermal method by mixing TiO2 precursor in aqueous solution of NaOH as solvent. The presence of the TiO2(B) nanowires into the polymer were confirmed by means of Field Emission Scanning Electron Microscopy, Fourier transform infrared and X-ray diffraction. The thermal study showed an increase of almost 20 °C in the maximum temperature of sPSU backbone decomposition due to the presence of 10 wt.% TiO2(B) nanowires. Water uptake also is improved with the presence of hydrophilic TiO2(B) nanowires. Proton conductivity of sPSU with 10 wt.% TiO2(B) nanowires was 21 mS cm-1 (at 85 °C and 100% RH). Under these experimental conditions the power density was 350 mW cm-2 similar to the value obtained for Nafion 117. Considering all these obtained results, the composite membrane doped with 10 wt.% TiO2(B) nanowires is a promising candidate as proton exchange electrolyte in fuel cells (PEMFCs), especially those operating at high temperatures.

From Green Technology to Functional Olive Oils: Assessing the Best Combination of Olive Tree-Related Extracts with Complementary Bioactivities.

Our aim was to assess the combination of olive tree-related extracts with the most favorable profile of in vitro bioactive properties. We tested the antioxidant (increment of low-density lipoprotein resistance against oxidation), vasoactive (promotion of nitric oxide release and decrease of endothelin-1 production in human umbilical vein endothelial cells), anti-inflammatory (decrease of the endothelial production of vascular cell adhesion molecule-1), and antithrombotic (reduction of the endothelial release of plasminogen activator inhibitor-1) capacities of six phenolic extracts and three triterpenic acid solutions (Ps and Ts, respectively). We tested extracts alone and in combination, at nutritional (Ps: 0.05-0.5 µmol/L; Ts: 0.001-0.1 µmol/L) and nutraceutical doses (Ps: 1-10 µmol/L; Ts: 0.25-10 µmol/L). The combination of Ps rich in 3,4-dihydroxyphenylglycol (76%, P2), hydroxytyrosol (95%, P3), and oleuropein (70%, P4) (final nutritional concentration: 0.15 µmol/L; final nutraceutical concentration: 3 µmol/L) was the best in order to prepare functional products and nutraceuticals with cardioprotective properties, despite the fact that the isolated extract with the greatest in vitro properties was P5 (75% oleocanthal), suggesting a potential synergistic effect among different olive components.

Synergistic Effect of 3',4'-Dihidroxifenilglicol and Hydroxytyrosol on Oxidative and Nitrosative Stress and Some Cardiovascular Biomarkers in an Experimental Model of Type 1 Diabetes Mellitus.

The objective of this study was to assess a possible synergistic effect of two extra-virgin olive oil polyphenols, 3,4,-dyhydroxyphenylglycol (DHPG) and hydroxytyrosol (HT), in an experimental model of type 1 diabetes. Seven groups of animals were studied: (1) Nondiabetic rats (NDR), (2) 2-month-old diabetic rats (DR), (3) DR treated with 5 mg/kg/day p.o. HT, (4) DR treated with 0.5 mg/kg/day p.o. DHPG, (5) DR treated with 1 mg/kg/day p.o. DHPG, (6) DR treated with HT + DHPG (0.5), (7) DR treated with HT + DHPG (1). Oxidative stress variables (lipid peroxidation, glutathione, total antioxidant activity, 8-isoprostanes, 8-hydroxy-2-deoxyguanosine, and oxidized LDL), nitrosative stress (3-nitrotyrosine), and some cardiovascular biomarkers (platelet aggregation, thromboxane B2, prostacyclin, myeloperoxidase, and vascular cell adhesion protein 1 (VCAM-1)) were analyzed. The diabetic animals showed an imbalance in all of the analyzed variables. HT exerted an antioxidant and downregulatory effect on prothrombotic biomarkers while reducing the fall of prostacyclin. DHPG presented a similar, but quantitatively lower, profile. HT plus DHPG showed a synergistic effect in the reduction of oxidative and nitrosative stress, platelet aggregation, production of prostacyclin, myeloperoxidase, and VCAM-1. This synergism could be important for the development of functional oils enriched in these two polyphenols in the proportion used in this study.

Extra Virgin Oil Polyphenols Improve the Protective Effects of Hydroxytyrosol in an In Vitro Model of Hypoxia-Reoxygenation of Rat Brain.

Hydroxytyrosol (HT) is the component primarily responsible for the neuroprotective effect of extra virgin olive oil (EVOO). However, it is less effective on its own than the demonstrated neuroprotective effect of EVOO, and for this reason, it can be postulated that there is an interaction between several of the polyphenols of EVOO. The objective of the study was to assess the possible interaction of four EVOO polyphenols (HT, tyrosol, dihydroxyphenylglycol, and oleocanthal) in an experimental model of hypoxia-reoxygenation in rat brain slices. The lactate dehydrogenase (LDH) efflux, lipid peroxidation, and peroxynitrite production were determined as measures of cell death, oxidative stress, and nitrosative stress, respectively. First, the polyphenols were incubated with the brain slices in the same proportions that exist in EVOO, comparing their effects with those of HT. In all cases, the cytoprotective and antioxidant effects of the combination were greater than those of HT alone. Second, we calculated the concentration-effect curves for HT in the absence or presence of each polyphenol. Tyrosol did not significantly modify any of the variables inhibited by HT. Dihydroxyphenylglycol only increased the cytoprotective effect of HT at 10 µM, while it increased its antioxidant effect at 50 and 100 µM and its inhibitory effect on peroxynitrite formation at all the concentrations tested. Oleocanthal increased the cytoprotective and antioxidant effects of HT but did not modify its inhibitory effect on nitrosative stress. The results of this study show that the EVOO polyphenols DHPG and OLC increase the cytoprotective effect of HT in an experimental model of hypoxia-reoxygenation in rat brain slices, mainly due to a possibly synergistic effect on HT's antioxidant action. These results could explain the greater neuroprotective effect of EVOO than of the polyphenols alone.