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Introduction We report the effects of plasma exchange (PE) with albumin replacement on neuropsychological, neuropsychiatric, and quality-of-life (QoL) outcomes in mild-to-moderate Alzheimer's disease (AD) patients in a phase 2b/3 trial (Alzheimer's Management by Albumin Replacement [AMBAR] study). Methods Three hundred forty-seven patients were randomized into placebo (sham-PE) and three PE-treatment arms with low/high doses of albumin, with/without intravenous immunoglobulin (IVIG). Specific test measurements were performed at baseline; month 2 (weekly conventional PE); months 6, 9, and 12 (monthly low-volume PE [LVPE]); and month 14. Results The PE-treated mild-AD cohort improved their language fluency and processing speed versus placebo at month 14 (effect sizes: >100%; P-values: .03 to .001). The moderate-AD cohort significantly improved short-term verbal memory (effect sizes: 94% to >100%; P-values: .02 to .003). The progression of the neuropsychiatric symptoms of PE-treated was similar to placebo. Mild-AD patients showed improved QoL (P-values: .04 to .008). Discussion PE-treated AD patients showed improvement in memory, language abilities, processing speed, and QoL-AD. No worsening of their psychoaffective status was observed.

BACKGROUND Crohn's disease (CD) with upper gastrointestinal involvement (UGI) may have a more aggressive and refractory course. However, evidence on this phenotype of patients is scarce. AIMS To identify the clinical characteristics, therapeutic requirements and complications associated with UGI in CD METHODS: Nationwide study of cases (UGI, UGI plus ileal/ileocolonic involvement) paired with controls (ileal/ileocolonic involvement) from the ENEIDA registry. Cases were matched to 2 controls by year of diagnosis ± 2.5 years. Patients with exclusive/predominant colonic location or complex perianal fistula were excluded. RESULTS Of 24 738 patients with CD in the ENEIDA registry, we identified 4058 with UGI (16% of the total CD cohort). Finally, 854 cases and 1708 controls were included. Cases were independently associated to extensive involvement (OR 2.7 [2.2-3.3], P

Introduction This phase 2b/3 trial examined the effects of plasma exchange (PE) in patients with mild‐to‐moderate Alzheimer's disease (AD). Methods Three hundred forty‐seven patients (496 screened) were randomized (1:1:1:1) into three PE treatment arms with different doses of albumin and intravenous immunoglobulin replacement (6‐week period of weekly conventional PE followed by a 12‐month period of monthly low‐volume PE), and placebo (sham). Results PE‐treated patients performed significantly better than placebo for the co‐primary endpoints: change from baseline of Alzheimer's Disease Cooperative Study–Activities of Daily Living (ADCS‐ADL; P = .03; 52% less decline) with a trend for Alzheimer's Disease Assessment Scale–Cognitive Subscale (ADAS‐Cog; P = .06; 66% less decline) scores at month 14. Moderate‐AD patients (baseline Mini‐Mental State Examination [MMSE] 18‐21) scored better on ADCS‐ADL (P = .002) and ADAS‐Cog (P = .05), 61% less decline both. There were no changes in mild‐AD patients (MMSE 22‐26). PE‐treated patients scored better on the Clinical Dementia Rating Sum of Boxes (CDR‐sb) (P = .002; 71% less decline) and Alzheimer's Disease Cooperative Study‐Clinical Global Impression of Change (ADCS‐CGIC) (P

In Europe, gastric adenocarcinoma (GADC) is commonly regarded as a disease of the elderly. This study aims to assess the proportion, characteristics, and survival of patients diagnosed with GADC under the age of 60.This is a retrospective, multicentric, and analytical study conducted at four tertiary Spanish hospitals. All patients diagnosed with GADC between 2008 and 2015 were included. Demographic, clinical, endoscopic, histologic, and survival data were retrieved. A multivariate analysis was performed to compare GADC in young (age≤60 years) and elderly patients.A total of 1374 patients with GADC were included. The mean age was 74 years (SD:11.1); 62.2% were males. There were 177 patients under the age of 60 (12.9%, 95% CI: 11.2-14.8%). GADC was frequently encountered as a metastatic disease in both young and elderly patients (Stage IV: 45.7% and 41%, respectively). In the multivariate analysis, alcohol abuse, ASA functional status I-II, diffuse subtype, neoadjuvant, and palliative therapy were independently associated (P0.05) with age ≤60 years. No differences were found in 2-year survival (GADC ≤60: 39% vs. 35%, P=0.45). Curative-intent surgery, TNM stage I-II, body mass index30kg/mOne out of eight cases of GADC were diagnosed under the age of 60. Metastatic disease was frequent at diagnosis and overall survival was poor regardless of age. Factors associated with localized disease correlated with improved survival in younger patients. Our results underline the need for early diagnosis strategies in our country.

We investigated the impact of diabetes mellitus (DM) in acute coronary syndrome (ACS) patients, and the 2-year prognosis based on antiplatelet therapy.This is a prospective and multicenter registry including hospitalized ACS patients. Clinical management and antiplatelet therapy at discharge were recorded. Bleeding events, all-cause mortality and major adverse cardiovascular events (MACEs) were recorded during 2-years and compared according to DM and the P2YFrom 1717 ACS patients, 653 (38%) had DM. Diabetic patients were older, more commonly females, with higher prevalence of comorbidities and more conservative management. After excluding antiplatelet monotherapy or oral anticoagulation, clopidogrel was prescribed in 59.6% of DM patients. Cox regression analysis showed that DM was an independent risk factor for MACE (aHR 1.39, 95% CI 1.05-1.83). The use of clopidogrel instead of ticagrelor/prasugrel was also independently associated with MACE (aHR 1.71, 95% CI 1.11-2.63), and all-cause mortality (aHR 2.47, 95% CI 1.23-4.96) in diabetic patients (log-rank p-values 0.001).In ACS patients, DM was associated with higher risk of MACE. In such patients, the use of ticagrelor/prasugrel reduced MACE and mortality compared to clopidogrel. Novel P2Y

Missed gastric cancer (MGC) is poorly documented in Mediterranean populations.(1) To assess the rate, predictors and survival of MGC. (2) To compare MGC and non-MGC tumors.This is a retrospective-cohort study conducted at four centers. MGC was defined as cancer detected within three years after negative esophagogastroduodenoscopy. Gastric adenocarcinomas diagnosed between 2008-2015 were included. Patients with no follow-up were excluded.During the study period 123,395 esophagogastroduodenoscopies were performed, with 1374 gastric cancers being diagnosed (1.1%). A total of 1289 gastric cancers were finally included. The overall rate of MGC was 4.7% (61/1289, 3.7-6%). A negative esophagogastroduodenoscopy in MGC patients was independently associated with PPI therapy (p 0.001), previous Billroth II anastomosis (p = 0.002), and lack of alarm symptoms (p 0.001). The most frequent location for MGC was the gastric body(52.4%). MGCs were smaller than non-MGCs (31 vs 41 mm, p = 0.047), more often flat or depressed (p = 0.003) and less likely to be encountered as advanced disease. Overall 2-year survival was similar between MGC (34.1%) and Non-MGC (35.3 %) (p = 0.59).MGC accounted for nearly five percent of newly-diagnosed gastric adenocarcinomas. Overall survival was poor and not different between MGC and non-MGC.

New sampling techniques to analyse lung diseases, such as exhaled breath condensate (EBC), are a breakthrough in research field since they are less invasive and less traumatic for the patients compared to lung biopsies. Nevertheless, there is an increasing need to optimize not only the sampling protocols but the storage and processing of specimens to get accurate results. Exhaled breath condensate was sampled employing the ECoScreen device. Concentrated protein was obtained after ultracentrifugation, lyophilization and reversed-phase chromatography. MALDI-time of flight (TOF)/TOF mass spectrometry (MS) was applied to determine the protein profile in EBC. Commercially available ELISA kits were used to detect the selected biomarker in the EBC after MALDI-MS proteins identification. The obtained EBC volume after two periods of 10 min doubled the amount obtained after 20 min. One hundred peptides were detected by MALDI-MS, and 18 proteins were identified after reversed-phase chromatography concentration. Dermcidin (P81605), S100A9 (P06702) and Cathepsin G (P08311) were selected to be analysed by ELISA. Dermcidin and S100A9 expression were statistically higher in lung cancer versus healthy volunteers. VEGF concentrations decreased, respectively, by 5.94 and 11.42-fold after 1 and 2 years of frozen EBC preservation in parallel with the declined number of proteins identified by MALDI-MS. Exhaled breath condensate analysis combined with MS technique may become a valuable method for lung cancer screening and Dermcidin and S100A9 may serve as biomarkers for lung cancer diagnosis or prognosis.

Introduction Autologous haematopoietic stem cell transplantation (AHSCT) is an accepted treatment in refractory Crohn's disease (CD). Material and methods Data on patients with refractory CD subjected to AHSCT are collected at the Hospital Universitario Ramon y Cajal in Madrid and the results obtained are described retrospectively. Results Seven patients in total have received AHSCT due to refractory CD in our centre. Three patients (43%) presented with clinical and endoscopic remission; one patient (14%) clinical improvement without remission and three patients (43%) remained active with the need to restart treatment in the assessment of the initial response to the AHSCT (after six months). Symptoms recurred in five of the seven patients (71%) and all of them had to restart medical treatment after an average of 13.8 months (range: 3–30 months). Only one patient needed surgery after the AHSCT. At the end of the follow-up, after a mean of 48 months (range: 17–78 months), 5/7 (71%) of the patients were in clinical remission with or without treatment. Conclusion AHSCT may be a promising therapeutic option for patients with refractory CD. Its usefulness lies in the fact that it can produce clinical remission without treatment in some patients, but also that it can make the disease treatable, obtaining a response to certain treatments in patients who had previously lost it.

Epistaxis in cirrhotic patients is a common issue. However, the literature published to date is very scarce.Retrospective case series of patients with cirrhosis who presented with a significant epistaxis, between 2006 and 2016.Data were collected from 39 cirrhotic patients with a mean age of 61.4 (±14) years, 75% of which were males. The main comorbidities were hypertension (33%) and diabetes mellitus (26%). Seven (18%) patients were taking antiplatelet drugs and 3 (8%) anticoagulants. One third of patients had a previous history of epistaxis and 6 had a previous ENT pathology. The main aetiological factor of cirrhosis was alcohol in 46% of cases, with 15 (38%) patients presenting with Child A, 12 (31%) Child B and 12 (31%) Child C class. The median MELD score upon admission was 16 [12-21]. Thirty-five (97%) patients had portal hypertension. At admission, the median platelet count was 89,000 [60,000-163,000] and mean INR was 1.52 (±0.37). Clinically, epistaxis presented as haematemesis or melaena in 8 (21%) patients, simulating gastrointestinal bleeding due to swallowing of blood. In 10 (26%) patients, epistaxis was considered as the probable trigger of an episode of hepatic encephalopathy. Two patients required ICU admission due to bleeding and 8 (21%) died during hospitalisation due to causes not directly related to epistaxis.Epistaxis is a complication to be taken into account in cirrhotic patients, as it can act as an encephalopathy trigger or simulate an episode of gastrointestinal bleeding.

Polar marine biota have adapted to thrive under one of the ocean’s most inhospitable scenarios, where extremes of temperature, light photoperiod and ice disturbance, along with ecological interactions, have selected species with a unique suite of secondary metabolites. Organisms of Arctic and Antarctic oceans are prolific sources of natural products, exhibiting wide structural diversity and remarkable bioactivities for human applications. Chemical skeletons belonging to terpene families are the most commonly found compounds, whereas cytotoxic antimicrobial properties, the capacity to prevent infections, are the most widely reported activities from these environments. This review firstly summarizes the regulations on access and benefit sharing requirements for research in polar environments. Then it provides an overview of the natural product arsenal from Antarctic and Arctic marine organisms that displays promising uses for fighting human disease. Microbes, such as bacteria and fungi, and macroorganisms, such as sponges, macroalgae, ascidians, corals, bryozoans, echinoderms and mollusks, are the main focus of this review. The biological origin, the structure of terpenes and terpenoids, derivatives and their biotechnological potential are described. This survey aims to highlight the chemical diversity of marine polar life and the versatility of this group of biomolecules, in an effort to encourage further research in drug discovery.

Background Increasing the interval of administration of anti-TNF agents over the duration specified in the data sheet is not common in inflammatory bowel disease (IBD). Aim To evaluate the outcomes of IBD patients treated with this strategy. Methods Patients with IBD who were treated with infliximab or adalimumab at intervals > 8 weeks or > 2 weeks, respectively, because of persistent clinical remission, were identified at local databases of the ENEIDA registry (a nationwide registry promoted by the Spanish Working Group in Crohn's disease and Ulcerative Colitis-GETECCU) of two referral centers. Treatment success was considered if patients remained in clinical remission with the same schedule or without biological therapy at the end of follow-up, and if no return to the conventional schedule, dose-escalation, change in biological agent, or a course of systemic corticosteroids or surgery were required. Results Eighty-five patients were included, 60 treated with infliximab and 25 with adalimumab. The spaced schedule was initiated after a median of 25 months on anti-TNF treatment (IQR 14-49). Throughout a median follow-up of 34 months (IQR 21-47), fifty patients (59%) fulfilled the success criteria of the spaced strategy. No differences were found regarding type of IBD or anti-TNF agent. Baseline C-reactive protein levels and disease duration at the time of starting anti-TNF treatment were the only factors associated with treatment success. Conclusions Anti-TNF administration at longer intervals than those provided in the data sheet may be an efficacious, convenient, and cheaper treatment option, particularly in patients in whom anti-TNF treatment was initiated early.

[Abstract] Objective. The purpose of this study was to evaluate the efficacy of a multimedia and interactive cognitive program on cognition and depressive symptomatology in healthy older adults. Methods. Adults aged ≥65 years were randomly assigned to two groups: the experimental group in which the participants received a computerized cognitive training application; and the control group in which the participants received no intervention during the protocol. Performance on the mini-mental state examination (MMSE) and the short-form of the geriatric depression scale (GDS-SF) were analysed using a three-way repeated-measure analysis of variance. Results. To determine cognition after the training, the cognitive program was used and the results were assessed using the MMSE, indicating that the significant time effects within the groups reflected the score for cognitive assessment that was significantly better after the intervention in the experimental group. No significant differences were observed with regard to the depressive symptomatology or between the groups according to sex or educational level on the two dimensions previously established (cognition and depressive symptomatology). Conclusion. The development of technological applications for intervention in older adults is increasing. Based on the established objective, we can conclude that the computerized intervention may constitute a good alternative to enhance the cognitive status in older people.

The Gram-negative Pantoea eucrina D2 was isolated from the marine sponge Chondrosia reniformis. Sponges were collected in a shallow volcanic vents system in Ischia island (South Italy), influenced by CO2 emissions and lowered pH. The chemical diversity of the secondary metabolites produced by this strain, under different culture conditions, was explored by a combined approach including molecular networking, pure compound isolation and NMR spectroscopy. The metabolome of Pantoea cf. eucrina D2 yielded a very complex molecular network, allowing the annotation of several metabolites, among them two biosurfactant clusters: lipoamino acids and surfactins. The production of each class of metabolites was highly dependent on the culture conditions, in particular, the production of unusual surfactins derivatives was reported for the first time from this genus, interestingly the production of these metabolites only arises by utilizing inorganic nitrogen as a sole nitrogen source. Major components of the extract obtained under standard medium culture conditions were isolated and identified as N-lipoamino acids by a combination of 1D and 2D NMR spectroscopy and HRESI-MS analysis. Assessment of the antimicrobial activity of the pure compounds towards some human pathogens, indicated a moderate activity of leucine containing N-lipoamino acids towards Staphylococcus aureus, Staphylococcus epidermidis and a clinical isolate of the emerging food pathogen Listeria monocytogenes.

This review is an overview on marine bioactive peptides with promising activities for the development of alternative drugs to fight human pathologies. In particular, we focus on potentially prolific producers of peptides in microorganisms, including sponge-associated bacteria and marine photoautotrophs such as microalgae and cyanobacteria. Microorganisms are still poorly explored for drug discovery, even if they are highly metabolically plastic and potentially amenable to culturing. This offers the possibility of obtaining a continuous source of bioactive compounds to satisfy the challenging demands of pharmaceutical industries. This review targets peptides because of the variety of potent biological activities demonstrated by these molecules, including antiviral, antimicrobial, antifungal, antioxidant, anticoagulant, antihypertensive, anticancer, antidiabetic, antiobesity, and calcium-binding bioactivities. Several of these peptides have already gained recognition as effective drug agents in recent years. We also focus on cutting-edge omic approaches for the discovery of novel compounds for pharmacological applications. With rapid depletion of natural resources, omic technologies may be the solution to efficiently produce a vast variety of novel peptides with unique pharmacological potential.

Solar radiation represents a key abiotic factor in the evolution of life in the oceans. In general, marine, biota—particularly in euphotic and dysphotic zones—depends directly or indirectly on light, but ultraviolet radiation (UV-R) can damage vital molecular machineries. UV-R induces the formation of reactive oxygen species (ROS) and impairs intracellular structures and enzymatic reactions. It can also affect organismal physiologies and eventually alter trophic chains at the ecosystem level. In Antarctica, physical drivers, such as sunlight, sea-ice, seasonality and low temperature are particularly influencing as compared to other regions. The springtime ozone depletion over the Southern Ocean makes organisms be more vulnerable to UV-R. Nonetheless, Antarctic species seem to possess analogous UV photoprotection and repair mechanisms as those found in organisms from other latitudes. The lack of data on species-specific responses towards increased UV-B still limits the understanding about the ecological impact and the tolerance levels related to ozone depletion in this region. The photobiology of Antarctic biota is largely unknown, in spite of representing a highly promising reservoir in the discovery of novel cosmeceutical products. This review compiles the most relevant information on photoprotection and UV-repair processes described in organisms from the Southern Ocean, in the context of this unique marine polar environment.

Anti-tumor necrosis factor agents (anti-TNF) drugs are commonly used in patients with inflammatory bowel disease (IBD) and have proven effective in both induction and maintenance therapy in luminal Crohn's disease and ulcerative colitis. Their efficacy has also been proven in fistulising perianal Crohn's disease. However, the evidence in other scenarios, such as stricturing, penetrating and non-fistulising perianal Crohn's disease, extraintestinal IBD manifestations and ileoanal reservoir complications, is not as robust. The aim of this review was to perform an analysis of the available literature and to determine the role of anti-TNF drugs in common clinical practice in patients affected by these complications.

Background: studies conducted in animal models and humans suggest the presence of a dynamic equilibrium of amyloid-β (Aβ) peptide between cerebrospinal fluid (CSF) and plasma compartments. Objective: to determine whether plasma exchange (PE) with albumin replacement was able to modify Aβ concentrations in CSF and plasma as well as to improve cognition in patients with mild-moderate Alzheimer's disease (AD). Methods: in a multicenter, randomized, patient- and rater-blind, controlled, parallel-group, phase II study, 42 AD patients were assigned (1 : 1) to PE treatment or control (sham) groups. Treated patients received a maximum of 18 PE with 5% albumin (Albutein®, Grifols) with three different schedules: two PE/weekly (three weeks), one PE/weekly (six weeks), and one PE/bi- weekly (12 weeks), plus a six-month follow-up period. Plasma and CSF Aβ1-40 and Aβ1-42 levels, as well as cognitive, functional, and behavioral measures were determined. Results: CSF Aβ1-42 levels after the last PE compared to baseline were marginally higher in PE-treated group versus controls (adjusted means of variation: 75.3 versus -45.5 pg/mL; 95% CI: -19.8, 170.5 versus 135.1, 44.2; p = 0.072). Plasma Aβ1-42 levels were lower in the PE-treated group after each treatment period (p

Clinical research [Abstract] BACKGROUND: The person with dementia should be treated as an unique person regarding symptoms directly associated with dementia, such as problems with memory, hallucinations, and delusions, as well as other physical, mental, or neurological deficits. The symptoms not directly typical of dementia, such as musculoskeletal disorders or depression, should be also be considered in order to improve the quality of life of a person with dementia. That is why professional caregivers have to broaden their current knowledge not only of medical symptoms but also of the patient’s psychosocial condition and increase their inquisitiveness about the individual condition of the patient. The aim of the study was to get to know the opinion of professional caregivers about the UnderstAID platform and its usefulness for informal caregivers. MATERIAL AND METHODS: Participants in the study group consisted of professional caregivers: nurses, sociologists, psychologists, physiotherapists, and occupational therapists, all of whom specialized in geriatrics and had experience in working with people with dementia. All professional caregivers answered 24 questions that refer to positive and negative aspects of the UnderstAID platform. RESULTS: The study group of professional caregivers highly appreciated that the application could give support to caregivers (mean score of 4.78; 5 points means that they totally agreed, and 1 point means that they totally disagreed) and that a wide range of multimedia materials helped the informal caregivers to gain a better understanding of the contents (mean score of 4.78). There was a statistically significant correlation between the age of the professional caregivers and the frequency of positive opinions that the UnderstAID application gave support to caregivers of relatives with dementia (p=0.028) and the opinion that videos, photos, and pictures may help the informal caregivers to gain a better understanding of the contents (p=0.028). CONCLUSIONS: A group of professional caregivers positively assessed the UnderstAID platform. Caregivers, especially older caregivers, highly appreciated the usefulness of videos, photos, and pictures for gaining a better understanding of the contents. European Commission; AAL5/1/2013 European Commission; AAL5/2/2013

Leire Lodeiro-Fernández, Laura Lorenzo-López, Ana Maseda, Laura Núñez-Naveira, José Luis Rodríguez-Villamil, José Carlos Millán-Calenti Gerontology Research Group, Department of Medicine, Faculty of Health Sciences, University of A Coruña, Campus of A Coruña, ACoruña, Spain Purpose: The possible relationship between audiometric hearing thresholds and cognitive performance on language tests was analyzed in a cross-sectional cohort of older adults aged ≥65 years (N=98) with different degrees of cognitive impairment.Materials and methods: Participants were distributed into two groups according to Reisberg’s Global Deterioration Scale (GDS): a normal/predementia group (GDS scores 1–3) and a moderate/moderately severe dementia group (GDS scores 4 and 5). Hearing loss (pure-tone audiometry) and receptive and production-based language function (Verbal Fluency Test, Boston Naming Test, and Token Test) were assessed.Results: Results showed that the dementia group achieved significantly lower scores than the predementia group in all language tests. A moderate negative correlation between hearing loss and verbal comprehension (r=-0.298; P

[Abstract] Objective. The prevalence of dementia is increasing and consequently the demands from families, institutions and healthcare system. Although a substantial amount of research on caregiving has emphasized the negative aspects of caregiving, specifically on caregiver burden and depression, less attention has been paid to the positive aspects of caregiving. The aim of the present work was to study the phenomenon of caregiving satisfaction in informal caregivers of people with dementia by assessing their likely predictors. Methods. A stress process model was used to study caregiver's satisfaction (measured using the Revised Caregiving Satisfaction Scale) on 101 informal caregivers of patients with dementia in relation to the caregiver's background and context, stress-related factors, and mediators. Results. The regression model has an adjusted R2 of 0.20, which indicates that having a consanguinity relationship with the care recipient, suffering from lower levels of subjective burden, and managing individuals with severe cognitive impairment are the most important predictors of higher caregiving satisfaction. Conclusion. Interventions focused on the enhancement of the caregiving satisfaction by increasing the understanding of the disease, should be especially addressed to caregivers without a consanguinity relationship and with high levels of subjective burden, and to those managing care recipients with mild or moderate stages of dementia. Ministerio de Industria, Energía y Turismo; AAL-2012-5-107

[Abstract] Objectives: To establish the possible relationship among three components of language (verbal fluency, naming and comprehension) and cognitive impairment as well as to determine the usefulness of language assessment tests to predict or monitor the development of cognitive impairment. Method: A comparative, descriptive and cross-sectional study was performed on 82 subjects 65 years of age who were cognitively assessed with the Mini Mental State Examination and were divided into two groups: Group A comprised of subjects classified as levels 1, 2 and 3 on the Reisberg’s Global Deterioration Scale (GDS) and group B comprised of subjects at levels 4 and 5 of the GDS. Language skills were assessed by the Verbal Fluency Test, Boston Naming Test and Token Test. Results: An inverse relationship between performance on language tests and cognitive impairment level was observed with a more pronounced effect observed on fluency and comprehension tests. Conclusion: Language assessments, especially fluency and comprehension, were good indicators of cognitive impairment. The use of these assessments as predictors of the degree of cognitive impairment is discussed in-depth.

Glycation and nitrotyrosination are pathological posttranslational modifications that make proteins prone to losing their physiological properties. Since both modifications are increased in Alzheimer's disease (AD) due to amyloid-β peptide (Aβ) accumulation, we have studied their effect on albumin, the most abundant protein in cerebrospinal fluid and blood. Brain and plasmatic levels of glycated and nitrated albumin were significantly higher in AD patients than in controls. In vitro turbidometry and electron microscopy analyses demonstrated that glycation and nitrotyrosination promote changes in albumin structure and biochemical properties. Glycated albumin was more resistant to proteolysis and less uptake by hepatoma cells occurred. Glycated albumin also reduced the osmolarity expected for a solution containing native albumin. Both glycation and nitrotyrosination turned albumin cytotoxic in a cell type-dependent manner for cerebral and vascular cells. Finally, of particular relevance to AD, these modified albumins were significantly less effective in avoiding Aβ aggregation than native albumin. In summary, nitrotyrosination and especially glycation alter albumin structural and biochemical properties, and these modifications might contribute for the progression of AD. This work was supported by the Spanish Ministry of Science and Innovation (SAF2012-38140; BIO2011-25039); Fondo de Investigación Sanitaria (PI10/00587; PI11/3035; and Red HERACLES RD06/0009, RD12/0042/0014); FEDER Funds; Generalitat de Catalunya (SGR05-266; SGR09-760); and Fundació la Marató de TV3 (100310). M.A.V. is the recipient of an ICREA Academia Award.

[Abstract] Background/aims It has been shown that cognitive training might help to protect against age-related cognitive decline. Our aim was to evaluate the efficacy of a computerized cognitive training application and its near transfer effects on the cognitive status of older adults. Methods Performance on the 7-Minute Screen at baseline and at the end of the program was analyzed by using a prepost design. Adults aged 55 and older (n = 101; mean age ± standard deviation: 68.97 ± 5.81 years) with and without memory impairments were trained. Results Significant improvements after the training program were found in memory, visuo-spatial and verbal fluency abilities, regardless of age, gender or education. Moreover, participants without significant memory impairments and those with Age-Associated Memory Impairment gained from the program more than subjects with mild cognitive impairment. Conclusion Computerized cognitive training programs, such as Telecognitio , may be used as a practical and valuable tool in clinic to improve cognitive status.

Exhaled breath condensate (EBC) is a representative sample from the lungs that may be used to detect different markers, but the reproducibility of these determinations is unknown over time. The aim of this paper is to assess the reproducibility of protein marker determination in EBC using samples collected at two different time points. EBC and blood were collected from 16 healthy subjects, smokers and non-smokers by using the ECoScreen device. EBC was collected on two separate occasions within ten days. Enzyme-linked immunosorbent assay (ELISA) was performed to measure angiogenesis and hypoxia markers. Blood and EBC samples were analyzed by ELISA to detect angiogenesis markers: vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and endostatin. A hypoxia marker, the anhydrase IX, was also determined. Biomarker concentration was higher in plasma samples compared to EBC. bFGF determination was higher in women (39.47 ± 3.914 versus 27.15 ± 3.145; p < 0.05). There were no significant differences among the averages of detection for any of the markers. The Bland-Altman method showed that the average of the differences or biases in EBC for every biomarker was close to zero, indicating a good reproducibility of the measurements. Nevertheless, the VEGF showed wide limits of agreement. EBC is suitable to detect biomarkers by ELISA and the measurements are reproducible over time. Nevertheless, some factors such as sex should be taken into account when analyzing the results.

Experimental animal models are necessary for studying asthma disease mechanisms and for identifying new therapeutic targets. We present a murine model of experimental asthma that allows integrated, quantitative assessment of airway inflammation and remodeling.BALB/c mice were sensitized to ovalbumin (OVA) and challenged with OVA or vehicle 3 times per week for 12 weeks.On bronchoalveolar lavage, the OVA-sensitized mice had significantly higher total leukocyte counts, with a median (Q25-Q75) of 670.0 cells/mL x 10(3) (376.2, 952.5) in comparison with 40.0 cells/mL x 10(3) (60.0-85.0) in controls (P=.001), and higher eosinophil and differential lymphocyte counts. In sagittal sections of lungs inflated to a standard pressure, the OVA-sensitized animals showed goblet cell hyperplasia in the respiratory epithelium (periodic acid-Schiff staining, 53.89 [36.26-62.84]cells/mm(2) vs 0.66 [0.00-1.06]cells/mm(2), P.001), dense mononuclear and eosinophilic inflammatory infiltrates (hematoxylin-eosin, 32.87 [27.34-37.13]eosinophils/mm(2) vs 0.06 [0.00-0.20]eosinophils/mm(2), P=.002), subepithelial infiltration by mast cells (toluidine blue, 2.88 [2.00-3.28] mast cells/mm(2) vs 0.28 [0.15-0.35] mast cells/mm(2), P.001), increased contractile tissue mass (immunofluorescence analysis for alpha-smooth-muscle actin, 2.60 [2.28-2.98] vs 1.08 [0.93-1.16], dimensionless, P.001) and enhanced extracellular matrix deposition (Masson's trichrome, 2.18 [1.85-2.80] vs 0.50 [0.37-0.65], dimensionless, P.001).Our dataset describes an experimental model of asthma which is driven by prolonged allergen exposure and in which airway inflammation and remodeling develop and are assessed together.

The aim of this study is to quantify the efficiency of the cognitive-behavioural treatment for smoking cessation in pregnancy and to evaluate the risk factors of success or failure for the abstinence before the childbirth.We studied 74 pregnant smoking women who, between January 2003 and January 2004, came to their obstetric regular control in the Hospital Casa Maternitat-Hospital Clínic i Provincial de Barcelona, and who voluntarily acceded to the cognitive-behavioural treatment without replacement of nicotine for the smoking cessation that they were offered.44% of women who made the program of visits came abstinent to the childbirth, and of them, 93.1% was abstinent during the quarantine. 51.5% reduced the consumption and 4.5% didn't change or increased the consumption. The fact that someone smokes at home (p = 0.006), the degree of dependence to the nicotine (p = 0.015) and a consumption of coffee superior to 3 daily cups (p = 0.039), in an equation of logistic regression, classified both groups (abstinence/not abstinence).The efficiency of a program based on cognitive-behavioural therapy, without replacement of nicotine, for the smoking cessation in the pregnancy is confirmed in our sample. We propose to consider risk factors of treatment failure the fact that someone smokes at home and a daily high consumption of coffee.

A clinical investigation program was carried out to replace endogenous albumin of patients with mild to moderate Alzheimer's disease (AD) with 5% Human Albumin Grifols(R) through a plasma exchange (PE) schedule, in order to alter the dynamic equilibrium between albumin-bound Abeta in plasma and Abeta in cerebrospinal fluid. In a pilot proof-of-concept study, 7 patients underwent 6 PE in 3 weeks and 1 year of follow-up. Plasma Abeta determinations demonstrated a variation pattern in levels in relation with the PEs. Cognitive status scores (MMSE and ADAS-Cog) were more stable than expected. In a phase II clinical trial, 29 patients were randomized into PEtreated and control groups with 1 year follow-up. Interim results point toward the occurrence of Abeta40 mobilization in the PE-treated patients, who scored better in cognitive tests (differences at 9 months: 2.5 in MMSE and 5.5 in ADAS-cog). These results suggest that a PE program with 5% Human Albumin Grifols may have a promising role in the treatment of mild to moderate AD.