Publications by authors named "Alberto Fernandez"

197 Publications

Modeling of H Permeation through Electroless Pore-Plated Composite Pd Membranes Using Computational Fluid Dynamics.

Membranes (Basel) 2021 Feb 9;11(2). Epub 2021 Feb 9.

Department of Chemical and Environmental Technology, Rey Juan Carlos University, C/Tulipán s/n, 28933 Móstoles, Spain.

This work focused on the computational fluid dynamics (CFD) modeling of H/N separation in a membrane permeator module containing a supported dense Pd-based membrane that was prepared using electroless pore-plating (ELP-PP). An easy-to-implement model was developed based on a source-sink pair formulation of the species transport and continuity equations. The model also included the Darcy-Forcheimer formulation for modeling the porous stainless steel (PSS) membrane support and Sieverts' law for computing the H permeation flow through the dense palladium film. Two different reactor configurations were studied, which involved varying the hydrogen flow permeation direction (in-out or out-in). A wide range of experimental data was simulated by considering the impact of the operating conditions on the H separation, such as the feed pressure and the H concentration in the inlet stream. Simulations of the membrane permeator device showed an excellent agreement between the predicted and experimental data (measured as permeate and retentate flows and H separation). Molar fraction profiles inside the permeator device for both configurations showed that concentration polarization near the membrane surface was not a limit for the hydrogen permeation but could be useful information for membrane reactor design, as it showed the optimal length of the reactor.
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http://dx.doi.org/10.3390/membranes11020123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915706PMC
February 2021

Half-Sandwich Ru(-cymene) Compounds with Diphosphanes: and Evaluation As Potential Anticancer Metallodrugs.

Inorg Chem 2021 Mar 11;60(5):2914-2930. Epub 2021 Feb 11.

Departamento de Química & Centro de Investigaciones Científicas Avanzadas (CICA), Universidade da Coruña, 15008 A Coruña, Spain.

Ruthenium(II) complexes are currently considered attractive alternatives to the widely used platinum-based drugs. We present herein the synthesis and characterization of half-sandwich ruthenium compounds formulated as [Ru(-cymene)(L)Cl][CFSO] (L = 1,1-bis(methylenediphenylphosphano)ethylene, ; L = 1,1-bis(diphenylphosphano)ethylene, ), which were characterized by elemental analysis, mass spectrometry, H and P{H} NMR, UV-vis and IR spectroscopy, conductivity measurements and cyclic voltammetry. The molecular structures for both complexes were determined by single-crystal X-ray diffraction. Their cytotoxic activity was evaluated using the MTT assay against human tumor cells, namely ovarian (A2780) and breast (MCF7 and MDA-MB-231). Both complexes were active against breast adenocarcinoma cells, with complex exhibiting a quite remarkable cytotoxicity in the submicromolar range. Interestingly, at concentrations equivalent to the IC values in the MCF7 cancer cells, complexes and presented lower cytotoxicity in normal human primary fibroblasts. The antiproliferative effects of and in MCF7 cells might be associated with the induction of reactive oxygen species (ROS), leading to a combined cell death mechanism via apoptosis and autophagy. Despite the fact that a partial intercalation between complexes and DNA was observed, no MCF7 cell cycle delay or arrest was observed, indicating that DNA might not be a direct target. Complexes and both exhibited a moderate to strong interaction with human serum albumin, suggesting that protein targets may be involved in their mode of action. Their acute toxicity was evaluated in the zebrafish model. Complex (the most toxic of the two) exhibited a lethal toxicity LC value about 1 order of magnitude higher than any IC concentrations found for the cancer cell models used, highlighting its therapeutic relevance as a drug candidate in cancer chemotherapy.
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http://dx.doi.org/10.1021/acs.inorgchem.0c02768DOI Listing
March 2021

Microbial community of Hyalomma lusitanicum is dominated by Francisella-like endosymbiont.

Ticks Tick Borne Dis 2021 Mar 14;12(2):101624. Epub 2020 Dec 14.

SaBio. Instituto de Investigación en Recursos Cinegéticos IREC-CSIC-UCLM-JCCM, Ronda de Toledo s/n, 13005, Ciudad Real, Spain; Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK 74078, USA.

Exploring tick associations with complex microbial communities and single-microbial partners, especially intracellular symbionts, has become crucial to understand tick biology. Of particular interest are the underlying interactions with biological consequences i.e. tick fitness, vector competence. In this study, we first sequenced the 16S rRNA bacterial phylogenetic marker in adult male ticks of Hyalomma lusitanicum collected from 5 locations in the province of Cáceres to explore the composition of its microbial community. Overall, 16S rRNA sequencing results demonstrated that the microbial community of H. lusitanicum is mostly dominated by Francisella-like endosymbionts (FLEs) (ranging from 52% to 99% of relative abundance) suggesting it is a key taxon within the microbial community and likely a primary endosymbiont. However, further research is required to explore the mechanisms underlying the interaction between FLEs and H. lusitanicum.
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http://dx.doi.org/10.1016/j.ttbdis.2020.101624DOI Listing
March 2021

Care bundle to reduce readmission in patients with heart failure: a modified Delphi consensus panel in Argentina.

BMJ Open 2020 12 29;10(12):e040028. Epub 2020 Dec 29.

Health Care Quality and Patient Safety, Institute for Clinical Effectiveness and Health Policy, Buenos Aires, Argentina.

Objectives: The aim of this study was to develop consensus among Argentine cardiologists on a care bundle to reduce readmissions of patients with heart failure (HF).

Setting: Hospitals and cardiology clinics in Argentina that provide in-hospital care for patients with HF.

Participants: Twenty-four cardiology experts participated in the two online rounds and 18 (75%) of them participated in the third-round meeting.

Methods: This study used a mixed-method design; it was conducted between August 2019 and January 2020. The development of a care bundle (a set of evidence-based interventions applied to improve clinical outcomes) involved three phases: (1) a literature review to define the list of interventions to be evaluated; (2) a modified Delphi panel to select interventions for the bundle and (3) definition of the HF care bundle. Also, the process included three rounds of scoring.

Results: Twenty-six interventions were evaluated. The interventions in the final bundle covered four categories: medication, continuum of care, lifestyle habits, predischarge tests. These were: medication: beta-blockers, angiotensin receptor neprilysin inhibitors or ACE-inhibitors, furosemide and antimineralocorticoids; continuum of care: follow-up appointment, daily weight monitoring; lifestyle habits: smoking cessation counselling and low-sodium diet; predischarge tests: renal function, ionogram, blood pressure control, echocardiogram and determination of decompensating cause.

Conclusion: Following a systematic mixed-method approach, we have developed a care bundle of interventions that could decrease readmission of patients with HF. The application of this bundle could contribute to scale evidence-based interventions.
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http://dx.doi.org/10.1136/bmjopen-2020-040028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7778781PMC
December 2020

Evaluation of Dust Deposition on Parabolic Trough Collectors in the Visible and Infrared Spectrum.

Sensors (Basel) 2020 Nov 2;20(21). Epub 2020 Nov 2.

Grupo TSK, C/Ada Byron, 220, 33203 Gijón, Asturias, Spain.

Solar energy is mostly harnessed in arid areas where a high concentration of atmospheric dust represents a major environmental degradation factor. Gravitationally settled particles and other solid particles on the surface of the photovoltaic panels or thermal collectors greatly reduce the absorbed solar energy. Therefore, frequent cleaning schedules are required, consuming high quantities of water in regions where water precipitation is rare. The efficiency of this cleaning maintenance is greatly improved when methods to estimate the degree of cleanness are introduced. This work focuses on the need for better detecting the degradation created by dust deposition, considering experimental data based on different air pollutants, and analyzing the resulting thermal and visible signatures under different operating environments. Experiments are performed using six different types of pollutants applied to the surface of parabolic trough collectors while varying the pollutant density. The resulting reflectivity in the visible and infrared spectrum is calculated and compared. Results indicate that the pollutants can be distinguished, although the reflectivity greatly depends on the combination of the particle size of the pollutant and the applied amount, with greater impact from pollutants with small particles.
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http://dx.doi.org/10.3390/s20216249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7662668PMC
November 2020

A multivariate model of time to conversion from mild cognitive impairment to Alzheimer's disease.

Geroscience 2020 12 4;42(6):1715-1732. Epub 2020 Sep 4.

Laboratory of Cognitive and Computational Neuroscience, Center for Biomedical Technology, Complutense University of Madrid and Polytechnic University of Madrid, Madrid, Spain.

The present study was aimed at determining which combination of demographic, genetic, cognitive, neurophysiological, and neuroanatomical factors may predict differences in time to progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD). To this end, a sample of 121 MCIs was followed up during a 5-year period. According to their clinical outcome, MCIs were divided into two subgroups: (i) the "progressive" MCI group (n = 46; mean time to progression 17 ± 9.73 months) and (ii) the "stable" MCI group (n = 75; mean time of follow-up 31.37 ± 14.58 months). Kaplan-Meier survival analyses were applied to explore each variable's relationship with the progression to AD. Once potential predictors were detected, Cox regression analyses were utilized to calculate a parsimonious model to estimate differences in time to progression. The final model included three variables (in order of relevance): left parahippocampal volume (corrected by intracranial volume, LP_ ICV), delayed recall (DR), and left inferior occipital lobe individual alpha peak frequency (LIOL_IAPF). Those MCIs with LP_ICV volume, DR score, and LIOL_IAPF value lower than the defined cutoff had 6 times, 5.5 times, and 3 times higher risk of progression to AD, respectively. Besides, when the categories of the three variables were "unfavorable" (i.e., values below the cutoff), 100% of cases progressed to AD at the end of follow-up. Our results highlighted the relevance of neurophysiological markers as predictors of conversion (LIOL_IAPF) and the importance of multivariate models that combine markers of different nature to predict time to progression from MCI to dementia.
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http://dx.doi.org/10.1007/s11357-020-00260-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732920PMC
December 2020

Discussion on Vuttipittayamongkol, P. and Elyan, E., Improved Overlap-Based Undersampling for Imbalanced Dataset Classification with Application to Epilepsy and Parkinson's Disease.

Int J Neural Syst 2020 Sep 23;30(9):2075001. Epub 2020 Jul 23.

DaSCI Andalusian Institute of Data Science and Computational Intelligence, University of Granada, Granada 18071, Spain.

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http://dx.doi.org/10.1142/S0129065720750015DOI Listing
September 2020

Learning the Edit Costs of Graph Edit Distance Applied to Ligand-Based Virtual Screening.

Curr Top Med Chem 2020 ;20(18):1582-1592

Department of Computer Engineering and Mathematics, Rovira i Virgili University, Tarragona, Spain.

Background: Graph edit distance is a methodology used to solve error-tolerant graph matching. This methodology estimates a distance between two graphs by determining the minimum number of modifications required to transform one graph into the other. These modifications, known as edit operations, have an edit cost associated that has to be determined depending on the problem.

Objective: This study focuses on the use of optimization techniques in order to learn the edit costs used when comparing graphs by means of the graph edit distance.

Methods: Graphs represent reduced structural representations of molecules using pharmacophore-type node descriptions to encode the relevant molecular properties. This reduction technique is known as extended reduced graphs. The screening and statistical tools available on the ligand-based virtual screening benchmarking platform and the RDKit were used.

Results: In the experiments, the graph edit distance using learned costs performed better or equally good than using predefined costs. This is exemplified with six publicly available datasets: DUD-E, MUV, GLL&GDD, CAPST, NRLiSt BDB, and ULS-UDS.

Conclusion: This study shows that the graph edit distance along with learned edit costs is useful to identify bioactivity similarities in a structurally diverse group of molecules. Furthermore, the target-specific edit costs might provide useful structure-activity information for future drug-design efforts.
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http://dx.doi.org/10.2174/1568026620666200603122000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7536799PMC
January 2020

Role of Magnetoencephalography in the Early Stages of Alzheimer Disease.

Neuroimaging Clin N Am 2020 May;30(2):217-227

Centro de Tecnología Biomédica, Campus de Montegancedo de la UPM, Pozuelo de Alarcón, Madrid 28223, Spain; Department of Legal Medicine, Psychiatry and Pathology, Complutense University of Madrid, Madrid, Spain.

As synaptic dysfunction is an early manifestation of Alzheimer disease (AD) pathology, magnetoencephalography (MEG) is capable of detecting disruptions by assessing the synchronized oscillatory activity of thousands of neurons that rely on the integrity of neural connections. MEG findings include slowness of the oscillatory activity, accompanied by a reduction of the alpha band power, and dysfunction of the functional networks. These findings are associated with the neuropathology of the disease and cognitive impairment. These neurophysiological biomarkers predict which patients with mild cognitive impairment will develop dementia. MEG has demonstrated its utility as a noninvasive biomarker for early detection of AD.
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http://dx.doi.org/10.1016/j.nic.2020.01.003DOI Listing
May 2020

Paternal and maternal mutations in X-STRs: A GHEP-ISFG collaborative study.

Forensic Sci Int Genet 2020 05 5;46:102258. Epub 2020 Feb 5.

Laboratório de Diagnóstico por DNA (LDD), Universidade do Estado do Rio de Janeiro, Brazil.

The GHEP-ISFG organized a collaborative study to estimate mutation rates for the markers included in the Investigator Argus X-12 QS kit Qiagen. A total of 16 laboratories gathered data from 1,612 father/mother/daughter trios, which were used to estimate both maternal and paternal mutation rates, when pooled together with other already published data. Data on fathers and mothers' age at the time of birth of the daughter were also available for ∼93 % of the cases. Population analyses were computed considering the genetic information of a subset of 1,327 unrelated daughters, corresponding to 2,654 haplotypes from residents in several regions of five countries: Argentina, Brazil, Ecuador, Portugal and Spain. Genetic differentiation analyses between the population samples from the same country did not reveal signs of significant stratification, although results from Hardy-Weinberg and linkage disequilibrium tests indicated the need of larger studies for Ecuador and Brazilian populations. The high genetic diversity of the markers resulted in a large number of haplotype combinations, showing the need of huge databases for reliable estimates of their frequencies. It should also be noted the high number of new alleles found, many of them not included in the allelic ladders provided with the kit, as very diverse populations were analyzed. The overall estimates for locus specific average mutation rates varied between 7.5E-04 (for DXS7423) and 1.1E-02 (for DXS10135), the latter being a troublesome figure for kinship analyses. Most of the found mutations (∼92 %) are compatible with the gain or loss of a single repeat. Paternal mutation rates showed to be 5.2 times higher than maternal ones. We also found that older fathers were more prone to transmit mutated alleles, having this trend not been observed in the case of the mothers.
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http://dx.doi.org/10.1016/j.fsigen.2020.102258DOI Listing
May 2020

Health-care costs of inflammatory bowel disease in a pan-European, community-based, inception cohort during 5 years of follow-up: a population-based study.

Lancet Gastroenterol Hepatol 2020 05 13;5(5):454-464. Epub 2020 Feb 13.

Department of Internal Medicine, Ben-Gurion University of the Negev, Beer Sheva, Israel.

Background: Inflammatory bowel disease (IBD) places a significant burden on health-care systems because of its chronicity and need for expensive therapies and surgery. With increasing use of biological therapies, contemporary data on IBD health-care costs are important for those responsible for allocating resources in Europe. To our knowledge, no prospective long-term analysis of the health-care costs of patients with IBD in the era of biologicals has been done in Europe. We aimed to investigate cost profiles of a pan-European, community-based inception cohort during 5 years of follow-up.

Methods: The Epi-IBD cohort is a community-based, prospective inception cohort of unselected patients with IBD diagnosed in 2010 at centres in 20 European countries plus Israel. Incident patients who were diagnosed with IBD according to the Copenhagen Diagnostic Criteria between Jan 1, and Dec 31, 2010, and were aged 15 years or older the time of diagnosis were prospectively included. Data on clinical characteristics and direct costs (investigations and outpatient visits, blood tests, treatments, hospitalisations, and surgeries) were collected prospectively using electronic case-report forms. Patient-level costs incorporated procedures leading to the initial diagnosis of IBD and costs of IBD management during the 5-year follow-up period. Costs incurred by comorbidities and unrelated to IBD were excluded. We grouped direct costs into the following five categories: investigations (including outpatient visits and blood tests), conventional medical treatment, biological therapy, hospitalisation, and surgery.

Findings: The study population consisted of 1289 patients with IBD, with 1073 (83%) patients from western Europe and 216 (17%) from eastern Europe. 488 (38%) patients had Crohn's disease, 717 (56%) had ulcerative colitis, and 84 (6%) had IBD unclassified. The mean cost per patient-year during follow-up for patients with IBD was €2609 (SD 7389; median €446 [IQR 164-1849]). The mean cost per patient-year during follow-up was €3542 (8058; median €717 [214-3512]) for patients with Crohn's disease, €2088 (7058; median €408 [133-1161]) for patients with ulcerative colitis, and €1609 (5010; median €415 [92-1228]) for patients with IBD unclassified (p<0·0001). Costs were highest in the first year and then decreased significantly during follow-up. Hospitalisations and diagnostic procedures accounted for more than 50% of costs during the first year. However, in subsequent years there was a steady increase in expenditure on biologicals, which accounted for 73% of costs in Crohn's disease and 48% in ulcerative colitis, in year 5. The mean annual cost per patient-year for biologicals was €866 (SD 3056). The mean yearly costs of biological therapy were higher in patients with Crohn's disease (€1782 [SD 4370]) than in patients with ulcerative colitis (€286 [1427]) or IBD unclassified (€521 [2807]; p<0·0001).

Interpretation: Overall direct expenditure on health care decreased over a 5-year follow-up period. This period was characterised by increasing expenditure on biologicals and decreasing expenditure on conventional medical treatments, hospitalisations, and surgeries. In light of the expenditures associated with biological therapy, cost-effective treatment strategies are needed to reduce the economic burden of inflammatory bowel disease.

Funding: Kirsten og Freddy Johansens Fond and Nordsjællands Hospital Forskningsråd.
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http://dx.doi.org/10.1016/S2468-1253(20)30012-1DOI Listing
May 2020

Corrigendum to "Physical activity effects on the individual alpha peak frequency of older adults with and without genetic risk factors for Alzheimer's Disease: A MEG study" [Clin. Neurophysiol. 129 (2018) 1981-1989].

Clin Neurophysiol 2020 Apr 28;131(4):983. Epub 2020 Jan 28.

Laboratory of Cognitive and Computational Neuroscience (UCM-UPM), Center for Biomedical Technology, Pozuelo de Alarcón, Spain; Department of Legal Medicine, Psychiatry and Pathology, Medical School, Universidad Complutense de Madrid, Spain.

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http://dx.doi.org/10.1016/j.clinph.2020.01.003DOI Listing
April 2020

Complexity changes in preclinical Alzheimer's disease: An MEG study of subjective cognitive decline and mild cognitive impairment.

Clin Neurophysiol 2020 02 6;131(2):437-445. Epub 2019 Dec 6.

Centre for Biomedical Engineering, Department of Mechanical Engineering Sciences, Faculty of Engineering and Physical Sciences, University of Surrey, Guildford GU2 7XH, UK.

Objective: To analyse magnetoencephalogram (MEG) signals with Lempel-Ziv Complexity (LZC) to identify the regions of the brain showing changes related to cognitive decline and Alzheimeŕs Disease (AD).

Methods: LZC was used to study MEG signals in the source space from 99 participants (36 male, 63 female, average age: 71.82 ± 4.06) in three groups (33 subjects per group): healthy (control) older adults, older adults with subjective cognitive decline (SCD), and adults with mild cognitive impairment (MCI). Analyses were performed in broadband (2-45 Hz) and in classic narrow bands (theta (4-8 Hz), alpha (8-12 Hz), low beta (12-20 Hz), high beta (20-30 Hz), and, gamma (30-45 Hz)).

Results: LZC was significantly lower in subjects with MCI than in those with SCD. Moreover, subjects with MCI had significantly lower MEG complexity than controls and SCD subjects in the beta frequency band. Lower complexity was correlated with smaller hippocampal volumes.

Conclusions: Brain complexity - measured with LZC - decreases in MCI patients when compared to SCD and healthy controls. This decrease is associated with a decrease in hippocampal volume, a key feature in AD progression.

Significance: This is the first study to date characterising the changes of brain activity complexity showing the specific spatial pattern of the alterations as well as the morphological correlations throughout preclinical stages of AD.
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http://dx.doi.org/10.1016/j.clinph.2019.11.023DOI Listing
February 2020

Recording behaviour of indoor-housed farm animals automatically using machine vision technology: A systematic review.

PLoS One 2019 23;14(12):e0226669. Epub 2019 Dec 23.

Department of Animal Science, Michigan State University, East Lansing, Michigan, United States of America.

Large-scale phenotyping of animal behaviour traits is time consuming and has led to increased demand for technologies that can automate these procedures. Automated tracking of animals has been successful in controlled laboratory settings, but recording from animals in large groups in highly variable farm settings presents challenges. The aim of this review is to provide a systematic overview of the advances that have occurred in automated, high throughput image detection of farm animal behavioural traits with welfare and production implications. Peer-reviewed publications written in English were reviewed systematically following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. After identification, screening, and assessment for eligibility, 108 publications met these specifications and were included for qualitative synthesis. Data collected from the papers included camera specifications, housing conditions, group size, algorithm details, procedures, and results. Most studies utilized standard digital colour video cameras for data collection, with increasing use of 3D cameras in papers published after 2013. Papers including pigs (across production stages) were the most common (n = 63). The most common behaviours recorded included activity level, area occupancy, aggression, gait scores, resource use, and posture. Our review revealed many overlaps in methods applied to analysing behaviour, and most studies started from scratch instead of building upon previous work. Training and validation sample sizes were generally small (mean±s.d. groups = 3.8±5.8) and in data collection and testing took place in relatively controlled environments. To advance our ability to automatically phenotype behaviour, future research should build upon existing knowledge and validate technology under commercial settings and publications should explicitly describe recording conditions in detail to allow studies to be reproduced.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0226669PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6927615PMC
April 2020

What electrophysiology tells us about Alzheimer's disease: a window into the synchronization and connectivity of brain neurons.

Neurobiol Aging 2020 01 19;85:58-73. Epub 2019 Sep 19.

Vertex Pharmaceuticals Incorporated, Boston, MA, USA.

Electrophysiology provides a real-time readout of neural functions and network capability in different brain states, on temporal (fractions of milliseconds) and spatial (micro, meso, and macro) scales unmet by other methodologies. However, current international guidelines do not endorse the use of electroencephalographic (EEG)/magnetoencephalographic (MEG) biomarkers in clinical trials performed in patients with Alzheimer's disease (AD), despite a surge in recent validated evidence. This position paper of the ISTAART Electrophysiology Professional Interest Area endorses consolidated and translational electrophysiological techniques applied to both experimental animal models of AD and patients, to probe the effects of AD neuropathology (i.e., brain amyloidosis, tauopathy, and neurodegeneration) on neurophysiological mechanisms underpinning neural excitation/inhibition and neurotransmission as well as brain network dynamics, synchronization, and functional connectivity, reflecting thalamocortical and corticocortical residual capacity. Converging evidence shows relationships between abnormalities in EEG/MEG markers and cognitive deficits in groups of AD patients at different disease stages. The supporting evidence for the application of electrophysiology in AD clinical research as well as drug discovery pathways warrants an international initiative to include the use of EEG/MEG biomarkers in the main multicentric projects planned in AD patients, to produce conclusive findings challenging the present regulatory requirements and guidelines for AD studies.
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http://dx.doi.org/10.1016/j.neurobiolaging.2019.09.008DOI Listing
January 2020

Neuropsychological and neurophysiological characterization of mild cognitive impairment and Alzheimer's disease in Down syndrome.

Neurobiol Aging 2019 12 3;84:70-79. Epub 2019 Aug 3.

Center for Biomedical Technology, Laboratory of Cognitive and Computational Neuroscience, Technical University of Madrid, Campus Montegancedo, Madrid, Spain; Department of Legal Medicine, Psychiatry and Pathology, Complutense University of Madrid, Spain, Madrid, Spain.

Down syndrome (DS) has been considered a unique model for the investigation of Alzheimer's disease (AD) but intermediate stages in the continuum are poorly defined. Considering this, we investigated the neurophysiological (i.e., magnetoencephalography [MEG]) and neuropsychological patterns of mild cognitive impairment (MCI) and AD in middle-aged adults with DS. The sample was composed of four groups: Control-DS (n = 14, mean age 44.64 ± 3.30 years), MCI-DS (n = 14, 51.64 ± 3.95 years), AD-DS (n = 13, 53.54 ± 6.58 years), and Control-no-DS (healthy controls, n = 14, 45.21 ± 4.39 years). DS individuals were studied with neuropsychological tests and MEG, whereas the Control-no-DS group completed only the MEG session. Our results showed that the AD-DS group exhibited a significantly poorer performance as compared with the Control-DS group in all tests. Furthermore, this effect was crucially evident in AD-DS individuals when compared with the MCI-DS group in verbal and working memory abilities. In the neurophysiological domain, the Control-DS group showed a widespread increase of theta activity when compared with the Control-no-DS group. With disease progression, this increased theta was substituted by an augmented delta, accompanied with a reduction of alpha activity. Such spectral pattern-specifically observed in occipital, posterior temporal, cuneus, and precuneus regions-correlated with the performance in cognitive tests. This is the first MEG study in the field incorporating both neuropsychological and neurophysiological information, and demonstrating that this combination of markers is sensitive enough to characterize different stages along the AD continuum in DS.
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http://dx.doi.org/10.1016/j.neurobiolaging.2019.07.017DOI Listing
December 2019

Sex Differences in the Complexity of Healthy Older Adults' Magnetoencephalograms.

Entropy (Basel) 2019 Aug 15;21(8). Epub 2019 Aug 15.

Laboratorio de Neurociencia Cognitiva y Computacional, Universidad Politécnica de Madrid-Universidad Complutense de Madrid (UPM-UCM), 28223 Madrid, Spain.

The analysis of resting-state brain activity recording in magnetoencephalograms (MEGs) with new algorithms of symbolic dynamics analysis could help obtain a deeper insight into the functioning of the brain and identify potential differences between males and females. Permutation Lempel-Ziv complexity (PLZC), a recently introduced non-linear signal processing algorithm based on symbolic dynamics, was used to evaluate the complexity of MEG signals in source space. PLZC was estimated in a broad band of frequencies (2-45 Hz), as well as in narrow bands (i.e., theta (4-8 Hz), alpha (8-12 Hz), low beta (12-20 Hz), high beta (20-30 Hz), and gamma (30-45 Hz)) in a sample of 98 healthy elderly subjects (49 males, 49 female) aged 65-80 (average age of 72.71 ± 4.22 for males and 72.67 ± 4.21 for females). PLZC was significantly higher for females than males in the high beta band at posterior brain regions including the precuneus, and the parietal and occipital cortices. Further statistical analyses showed that higher complexity values over highly overlapping regions than the ones mentioned above were associated with larger hippocampal volumes only in females. These results suggest that sex differences in healthy aging can be identified from the analysis of magnetoencephalograms with novel signal processing methods.
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http://dx.doi.org/10.3390/e21080798DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7515326PMC
August 2019

Effects of storage over a 36-month period on coagulation factors in a canine plasma product obtained by use of plasmapheresis.

Am J Vet Res 2019 Jun;80(6):578-585

Objective: To evaluate stability of coagulation factors in canine plasma obtained by use of plasmapheresis and stored over a 36-month period.

Sample: Canine plasma obtained by use of plasmapheresis acquired from a commercial blood bank.

Procedures: Coagulation testing for fibrinogen concentration and activity of factors II, V, VII, VIII, and IX and von Willebrand factor was performed on canine plasma obtained by use of plasmapheresis. Samples were obtained for testing at 6-month intervals from plasma stored for up to 36 months.

Results: A simple mixed linear regression model was created for each analysis. Median value for the fibrinogen concentration was > 150 mg/dL for all time points, except at 467, 650, and 1,015 days of storage. Median value for factor VIII was > 70% only at 650 days. Median value for factor V was > 50% through 650 days. Median value for factors VII and X was > 50% through 833 days, and median value for factors II and VII was > 50% through 1,015 days. Median value for von Willebrand factor was > 50% for the entire study (1,198 days). Median value for factor X was always < 50%.

Conclusions And Clinical Relevance: Coagulation factors degraded over time at variable rates, and all labile factors remained at > 50% activity for longer than 1 year. Plasma collected by plasmapheresis potentially offers prolonged life span of some clotting factors. Plasmapheresis is an acceptable form of canine plasma collection for transfusion purposes, and further studies should be performed to determine all of its benefits.
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http://dx.doi.org/10.2460/ajvr.80.6.578DOI Listing
June 2019

Initiation of sacubitril/valsartan in haemodynamically stabilised heart failure patients in hospital or early after discharge: primary results of the randomised TRANSITION study.

Eur J Heart Fail 2019 08 27;21(8):998-1007. Epub 2019 May 27.

Cardiology Department, Hospital Universitario Virgen de la Arrixaca, Universidad de Murcia, Murcia, Spain.

Aims: To assess tolerability and optimal time point for initiation of sacubitril/valsartan in patients stabilised after acute heart failure (AHF).

Methods And Results: TRANSITION was a randomised, multicentre, open-label study comparing two treatment initiation modalities of sacubitril/valsartan. Patients aged ≥ 18 years, hospitalised for AHF were stratified according to pre-admission use of renin-angiotensin-aldosterone system inhibitors and randomised (n = 1002) after stabilisation to initiate sacubitril/valsartan either ≥ 12-h pre-discharge or between Days 1-14 post-discharge. Starting dose (as per label) was 24/26 mg or 49/51 mg bid with up- or down-titration based on tolerability. The primary endpoint was the proportion of patients attaining 97/103 mg bid target dose after 10 weeks. Median time of first dose of sacubitril/valsartan from the day of discharge was Day -1 and Day +1 in the pre-discharge group and the post-discharge group, respectively. Comparable proportions of patients in the pre- and post-discharge initiation groups met the primary endpoint [45.4% vs. 50.7%; risk ratio (RR) 0.90; 95% confidence interval (CI) 0.79-1.02]. The proportion of patients who achieved and maintained for ≥ 2 weeks leading to Week 10, either 49/51 or 97/103 mg bid was 62.1% vs. 68.5% (RR 0.91; 95% CI 0.83-0.99); or any dose was 86.0% vs. 89.6% (RR 0.96; 95% CI 0.92-1.01). Discontinuation due to adverse events occurred in 7.3% vs. 4.9% of patients (RR 1.49; 95% CI 0.90-2.46).

Conclusions: Initiation of sacubitril/valsartan in a wide range of heart failure with reduced ejection fraction patients stabilised after an AHF event, either in hospital or shortly after discharge, is feasible with about half of the patients achieving target dose within 10 weeks.

Clinical Trial Registration: ClinicalTrials.gov ID: NCT02661217.
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http://dx.doi.org/10.1002/ejhf.1498DOI Listing
August 2019

Ligand-Based Virtual Screening Using Graph Edit Distance as Molecular Similarity Measure.

J Chem Inf Model 2019 04 10;59(4):1410-1421. Epub 2019 Apr 10.

Departament d'Enginyeria Informàtica i Matemàtiques , Universitat Rovira i Virgili , Tarragona , Catalunya 43007 , Spain.

Extended reduced graphs provide summary representations of chemical structures using pharmacophore-type node descriptions to encode the relevant molecular properties. Commonly used similarity measures using reduced graphs convert these graphs into 2D vectors like fingerprints, before chemical comparisons are made. This study investigates the effectiveness of a graph-only driven molecular comparison by using extended reduced graphs along with graph edit distance methods for molecular similarity calculation as a tool for ligand-based virtual screening applications, which estimate the bioactivity of a chemical on the basis of the bioactivity of similar compounds. The results proved to be very stable and the graph editing distance method performed better than other methods previously used on reduced graphs. This is exemplified with six publicly available data sets: DUD-E, MUV, GLL&GDD, CAPST, NRLiSt BDB, and ULS-UDS. The screening and statistical tools available on the ligand-based virtual screening benchmarking platform and the RDKit were also used. In the experiments, our method performed better than other molecular similarity methods which use array representations in most cases. Overall, it is shown that extended reduced graphs along with graph edit distance is a combination of methods that has numerous applications and can identify bioactivity similarities in a structurally diverse group of molecules.
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http://dx.doi.org/10.1021/acs.jcim.8b00820DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6668628PMC
April 2019

Corrigendum: The Importance of the Validation of M/EEG With Current Biomarkers in Alzheimer's Disease.

Front Hum Neurosci 2019 6;13:81. Epub 2019 Mar 6.

McGovern Medical School University of Texas Health Science Center, Houston, TX, United States.

[This corrects the article DOI: 10.3389/fnhum.2019.00017.].
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http://dx.doi.org/10.3389/fnhum.2019.00081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6415698PMC
March 2019

The Importance of the Validation of M/EEG With Current Biomarkers in Alzheimer's Disease.

Front Hum Neurosci 2019 5;13:17. Epub 2019 Feb 5.

Electrical Engineering and Bioengineering Lab, Department of Industrial Engineering & IUNE Universidad de La Laguna, Tenerife, Spain.

Current biomarkers used in research and in clinical practice in Alzheimer's Disease (AD) are the analysis of cerebral spinal fluid (CSF) to detect levels of Aβ42 and phosphorylated-tau, amyloid and FDG-PET, and MRI volumetry. Some of these procedures are still invasive for patients or expensive. Electroencephalography (EEG) and Magnetoencephalography (MEG) are two non-invasive techniques able to detect the early synaptic dysfunction and track the course of the disease. However, in spite of its added value they are not part of the standard of care in clinical practice in dementia. In this paper we review what these neurophysiological techniques can add to the early diagnosis of AD, whether results in both modalities are related to each other or not, as well as the need of its validation against current biomarkers. We discuss their potential implications for the better understanding of the pathophysiological mechanisms of the disease as well as the need of performing simultaneous M/EEG recordings to better understand discrepancies between these two techniques. Finally, more studies are needed studying M/EEG with amyloid and Tau biomarkers.
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http://dx.doi.org/10.3389/fnhum.2019.00017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6374629PMC
February 2019

Impact of origin-destination information in epidemic spreading.

Sci Rep 2019 02 19;9(1):2315. Epub 2019 Feb 19.

Department Enginyeria Informàtica i Matemàtiques, Universitat Rovira i Virgili, 43007, Tarragona, Spain.

The networked structure of contacts shapes the spreading of epidemic processes. Recent advances on network theory have improved our understanding of the epidemic processes at large scale. The relevance of several considerations still needs to be evaluated in the study of epidemic spreading. One of them is that of accounting for the influence of origin and destination patterns in the flow of the carriers of an epidemic. Here we compute origin-destination patterns compatible with empirical data of coarse grained flows in the air transportation network. We study the incidence of epidemic processes in a metapopulation approach considering different alternatives to the flows prior knowledge. The data-driven scenario where the estimation of origin and destination flows is considered turns out to be relevant to assess the impact of the epidemics at a microscopic level (in our scenario, which populations are infected). However, this information is irrelevant to assess its macroscopic incidence (fraction of infected populations). These results are of interest to implement even better computational platforms to forecast epidemic incidence.
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http://dx.doi.org/10.1038/s41598-019-38722-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6381217PMC
February 2019

Vogt-Koyanagi-Harada Disease, a Rare Entity in Spain: The Challenge of Worldwide Immigration and Globalization.

Eur J Case Rep Intern Med 2018 26;5(7):000886. Epub 2018 Jul 26.

Ophthalmology Department, Baza Hospital, Granada, Spain.

Vogt-Koyanagi-Harada disease is rare, mediated by autoimmune melanocyte inflammation and facilitated by genetic predisposition. The main clinical features include uveitis, meningitis, tinnitus and sensorineural deafness, and skin and hair depigmentation. It usually develops in four consecutive stages: prodromal, acute uveitic, convalescent, and chronic or recurrent. In view of the first two stages, the differential diagnosis takes into account uveo-meningeal syndromes. Treatment is based on high dose corticosteroids. We present the case of a 14-year-old girl admitted to hospital with fever, progressive uveo-meningeal symptoms, and sensorineural hearing loss. After work-up, the final diagnosis of Vogt-Koyanagi-Harada disease was made.

Learning Points: Vogt-Koyanagi-Harada disease should be considered when a patient presents with uveo-meningeal syndromes, particularly in pigmented ethnic groups.Acute bilateral uveitis should raise suspicion of Vogt-Koyanagi-Harada disease.Early stage diagnosis leads to prompt appropriate treatment and improves patient outcomes.
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http://dx.doi.org/10.12890/2018_000886DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6346778PMC
July 2018

Modern neuropsychological tests for a diversity of cultural contexts.

Clin Neuropsychol 2019 02 21;33(2):438-445. Epub 2019 Jan 21.

a Universidad Católica de Córdoba - Cortex Foundation-Universidad Nacional de Córdoba , Córdoba , Argentina.

Objective: The appropriateness of the current neuropsychological tests for the assessment of different populations has been questioned. In this issue several articles have proposed the modernization of neuropsychological testing by incorporating modern technological devices such as computers, mobile phones, or tablets. This is a commentary on the articles contained in the special issue about the inclusion of modern assessment methods that can be properly used around the world and not only in technologically/economically advanced countries.

Methods: The author of this article reviewed the articles included in the special issue with the goal of commenting on whether the new approaches proposed would have global relevance and applicability.

Results: The use of biomedical databases and modern technological devices such as computers, wearables and tablets might not be available in many countries, thus leading to a situation in which modern neuropsychological tests might be available only in some world regions. In addition, because in many countries there are large percentages of population with low education these modern neuropsychological tests might not be appropriate for them. Finally, tests developed with culturally specific stimuli will not be applicable in some cultures.

Conclusion: This article provides an overview of several issues that should be considered to make neuropsychological tests both modern and accessible around the world, more specifically the cross-cultural appropriateness and accessibility for low educated individuals and availability in low/middle income regions.
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http://dx.doi.org/10.1080/13854046.2018.1560501DOI Listing
February 2019

Current trends in the management of canine traumatic brain injury: An Internet-based survey.

Can Vet J 2019 01;60(1):73-79

Cape Cod Veterinary Specialists, 11 Bourne Bridge Approach Street, Bourne, Massachusetts, USA.

This study characterized trends in management of canine traumatic brain injury (TBI) among 182 small animal veterinarians grouped as follows: Board-certified specialists at a veterinary teaching hospital (BCS-VTH), Board-certified specialists in private practice (BCS-PP), non-specialists at a teaching hospital (DVM-VTH), and non-specialists in private practice (DVM-PP). The BCS-VTH, BSC-PP, and DVM-VTH groups were more comfortable using the modified Glasgow Coma Scale (MGCS) than the DVM-PP group ( < 0.001, < 0.001, and = 0.009, respectively). All respondents chose the following diagnostics most frequently: packed cell volume/total solids (95.6%), blood glucose (96.7%), and blood pressure (95.0%). The DVM-VTH group chose the following more frequently than the DVM-PP group: computed tomography (19.4% 4.5%; = 0.027), venous or arterial blood gas (83.9% 46.3%; < 0.001), electrocardiography (71.0% 44.8%; = 0.018), lactate (87.1% 59.7%; = 0.009), and brief thoracic ultrasound (87.1% 62.7%; = 0.017). BCS-PP chose hypertonic saline more frequently than DVM-PP (94.1% 74.6%; = 0.005). The DVM-PP group chose corticosteroid therapy and anticonvulsant therapy more frequently than BCS-PP (10.4% 0.0%; = 0.019; 73.1% 43.1%; = 0.004, respectively). This study highlights variability in management of canine TBI.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6294016PMC
January 2019

Ru( p-cymene) Compounds as Effective and Selective Anticancer Candidates with No Toxicity in Vivo.

Inorg Chem 2018 Nov 19;57(21):13150-13166. Epub 2018 Oct 19.

Departamento de Química & Centro de Investigaciones Científicas Avanzadas (CICA) , Universidade da Coruña , 15008 A Coruña , Spain.

Ruthenium(II) complexes are currently considered a viable alternative to the widely used platinum complexes as efficient anticancer agents. We herein present the synthesis and characterization of half-sandwich ruthenium compounds with the general formula [Ru( p-cymene)(L-N,N)Cl][CFSO] (L = 3,6-di-2-pyridyl-1,2,4,5-tetrazine (1) 6,7-dimethyl-2,3-bis(pyridin-2-yl)quinoxaline (2)), which have been synthesized by substitution reactions from the precursor dimer [Ru( p-cymene)(Cl)(μ-Cl)] and were characterized by elemental analysis, mass spectrometry, H NMR, UV-vis, and IR spectroscopy, conductivity measurements, and cyclic voltammetry. The molecular structure for complex 2 was determined by single-crystal X-ray diffraction. The cytotoxic activity of these compounds was evaluated against human tumor cells, namely ovarian carcinoma A2780 and breast MCF7 and MDAMB231 adenocarcinoma cells, and against normal primary fibroblasts. Whereas the cytotoxic activity of 1 is moderate, IC values found for 2 are among the lowest previously reported for Ru( p-cymene) complexes. Both compounds present no cytotoxic effect in normal human primary fibroblasts when they are used at the IC concentration in A2780 and MCF7 cancer cells. Their antiproliferative capacity is associated with a combined mechanism of apoptosis and autophagy. A strong interaction with DNA was observed for both with a binding constant value of the same magnitude as that of the classical intercalator [Ru(phen)(dppz)]. Both complexes bind to human serum albumin with moderate to strong affinity, with conditional binding constants (log K) of 4.88 for complex 2 and 5.18 for complex 1 in 2% DMSO/10 mM Hepes pH7.0 medium. The acute toxicity was evaluated in zebrafish embryo model using the fish embryo acute toxicity test (FET). Remarkably, our results show that compounds 1 and 2 are not toxic/lethal even at extremely high concentrations. The novel compounds reported herein are highly relevant antitumor metallodrug candidates, given their in vitro cytotoxicity toward cancer cells and the lack of in vivo toxicity.
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http://dx.doi.org/10.1021/acs.inorgchem.8b01270DOI Listing
November 2018

Val66Met Polymorphism and Gamma Band Disruption in Resting State Brain Functional Connectivity: A Magnetoencephalography Study in Cognitively Intact Older Females.

Front Neurosci 2018 2;12:684. Epub 2018 Oct 2.

Laboratory of Cognitive and Computational Neuroscience, Center for Biomedical Technology, Universidad Complutense and Universidad Politécnica de Madrid, Madrid, Spain.

The pathophysiological processes undermining brain functioning decades before the onset of the clinical symptoms associated with dementia are still not well understood. Several heritability studies have reported that the Brain Derived Neurotrophic Factor () Val66Met genetic polymorphism could contribute to the acceleration of cognitive decline in aging. This mutation may affect brain functional connectivity (FC), especially in those who are carriers of the Met allele. The aim of this work was to explore the influence of the Val66Met polymorphism in whole brain eyes-closed, resting-state magnetoencephalography (MEG) FC in a sample of 36 cognitively intact (CI) older females. All of them were ε3ε3 homozygotes for the apolipoprotein E () gene and were divided into two subgroups according to the presence of the Met allele: Val/Met group ( = 16) and Val/Val group ( = 20). They did not differ in age, years of education, Mini-Mental State Examination scores, or normalized hippocampal volumes. Our results showed reduced antero-posterior gamma band FC within the Val/Met genetic risk group, which may be caused by a GABAergic network impairment. Despite the lack of cognitive decline, these results might suggest a selective brain network vulnerability due to the carriage of the Met allele, which is linked to a potential progression to dementia. This neurophysiological signature, as tracked with MEG FC, indicates that age-related brain functioning changes could be mediated by the influence of particular genetic risk factors.
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http://dx.doi.org/10.3389/fnins.2018.00684DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6176075PMC
October 2018

Physical activity effects on the individual alpha peak frequency of older adults with and without genetic risk factors for Alzheimer's Disease: A MEG study.

Clin Neurophysiol 2018 09 11;129(9):1981-1989. Epub 2018 Jul 11.

Laboratory of Cognitive and Computational Neuroscience (UCM-UPM), Center for Biomedical Technology, Pozuelo de Alarcón, Spain; Department of Legal Medicine, Psychiatry and Pathology, Medical School, Universidad Complutense de Madrid, Spain.

Objective: Since a cure for Alzheimer's Disease (AD) is yet to be discovered, attention has shifted towards prevention. Physical activity (PA) emerged as a notorious lifestyle factor that could influence brain structure and function. The individual alpha peak frequency (IAPF) is a measure that summarizes the spectral content of brain signals and has been proven to be sensitive to both AD pathology and PA interventions. Therefore, our goal was to unravel whether chronic PA modulates IAPF and if APOE ɛ4 carriage moderates this relationship.

Methods: We analyzed 4-minutes of resting-state magnetoencephalographic recordings from 100 healthy elders that provided self-reported measures of PA, and the IAPF was calculated.

Results: We found that IAPF was negatively influenced by age and APOE and positively influenced by PA. The effect of PA on IAPF only remained significant for the ɛ4 non-carriers group.

Conclusions: PA is positively associated to higher IAPF in healthy older adults and could potentially act as a protective factor against cognitive decline. Nevertheless, such effect is non-significant among elders who are more vulnerable to developing AD due to their genetic carriage.

Significance: This investigation offers the first neurophysiological evidences on the combined effects of APOE genotype and PA in healthy elders.
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http://dx.doi.org/10.1016/j.clinph.2018.06.026DOI Listing
September 2018

Complexity Changes in Brain Activity in Healthy Ageing: A Permutation Lempel-Ziv Complexity Study of Magnetoencephalograms.

Entropy (Basel) 2018 Jul 3;20(7). Epub 2018 Jul 3.

Centre for Biomedical Engineering, Department of Mechanical Engineering Sciences, Faculty of Engineering and Physical Sciences, University of Surrey, Guildford GU2 7XH, UK.

Maturation and ageing, which can be characterised by the dynamic changes in brain morphology, can have an impact on the physiology of the brain. As such, it is possible that these changes can have an impact on the magnetic activity of the brain recorded using magnetoencephalography. In this study changes in the resting state brain (magnetic) activity due to healthy ageing were investigated by estimating the complexity of magnetoencephalogram (MEG) signals. The main aim of this study was to identify if the complexity of background MEG signals changed significantly across the human lifespan for both males and females. A sample of 177 healthy participants (79 males and 98 females aged between 21 and 80 and grouped into 3 categories i.e., early-, mid- and late-adulthood) was used in this investigation. This investigation also extended to evaluating if complexity values remained relatively stable during the 5 min recording. Complexity was estimated using permutation Lempel-Ziv complexity, a recently introduced complexity metric, with a motif length of 5 and a lag of 1. Effects of age and gender were investigated in the MEG channels over 5 brain regions, i.e., anterior, central, left lateral, posterior, and, right lateral, with highest complexity values observed in the signals recorded by the channels over the anterior and central regions of the brain. Results showed that while changes due to age had a significant effect on the complexity of the MEG signals recorded over 5 brain regions, gender did not have a significant effect on complexity values in all age groups investigated. Moreover, although some changes in complexity were observed between the different minutes of recording, due to the small magnitude of the changes it was concluded that practical significance might outweigh statistical significance in this instance. The results from this study can contribute to form a fingerprint of the characteristics of healthy ageing in MEGs that could be useful when investigating changes to the resting state activity due to pathology.
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http://dx.doi.org/10.3390/e20070506DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7513026PMC
July 2018