100 research outputs found

    Changes in brain activity related to episodic memory retrieval in adults with single domain amnestic mild cognitive impairment

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    The present fMRI study aimed to characterize the performance and the brain activity changes related to episodic memory retrieval in adults with single domain aMCI (sdaMCI), relative to cognitively unimpaired adults. Participants performed an old/new recognition memory task with words while BOLD signal was acquired. The sdaMCI group showed lower hits (correct recognition of old words), lower ability to discriminate old and new words, higher errors and longer reaction times for hits. This group also displayed brain hypoactivation in left precuneus and the left midcingulate cortex during the successful recognition of old words. These changes in brain activity suggest the presence of neural dysregulations in brain regions involved during successful episodic memory retrieval. Moreover, hypoactivation in these brain areas discriminated both groups with moderate sensitivity and specificity values, suggesting that it might constitute a potential neurocognitive biomarker of sdaMCIThis study was supported by grants from the Spanish Government, Ministerio de Economía y Competitividad (PSI2014–55316-C3–3-R; PSI2017–89389-C2–2-R; PID2020–114521RB-C21/C22); and the Galician Government, Axudas para a Consolidación e Estruturación de Unidades de Investigación Competitivas do Sistema Universitario de Galicia: GRC (GI-1807-USC. Ref: ED431–2017/27; ED431C-2021/04. All with ERDF/FEDER fundsS

    Spatiotemporal pattern of brain electrical activity related to immediate and delayed episodic memory retrieval

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    In the present study we used the event-related brain potentials (ERP) technique and eLORETA (exact low-resolution electromagnetic tomography) method in order to characterize and compare the performance and the spatiotemporal pattern of the brain electrical activity related to the immediate episodic retrieval of information (words) that is being learned relative to delayed episodic retrieval twenty-minutes later. For this purpose, 16 young participants carried out an old/new word recognition task with source memory (word colour). The task included an immediate memory phase (with three study-test blocks) followed (20 min later) by a delayed memory phase with one test block. The behavioural data showed progressive learning and consolidation of the information (old words) during the immediate memory phase. The ERP data to correctly identified old words for which the colour was subsequently recollected (H/H) compared to the correctly rejected new words (CR) showed: (1) a significant more positive-going potential in the 500–675 ms post-stimulus interval (parietal old/new effect, related to recollection), and (2) a more negative-going potential in the 950–1850 ms interval (LPN effect, related to retrieval and post-retrieval processes). The eLORETA data also revealed that the successful recognition of old words (and probably retrieval of their colour) was accompanied by activation of (1) left medial temporal (parahippocampal gyrus) and parietal regions involved in the recollection in both memory phases, and (2) prefrontal regions and the superior temporal gyrus (in the immediate and delayed memory phases respectively) involved in monitoring, evaluating and maintaining the retrieval products. These findings indicate that episodic memory retrieval depends on a network involving medial temporal lobe and frontal, parietal and temporal neocortical structures. That network was involved in immediate and delayed memory retrieval and during the course of memory consolidation, with greater activation of some nodes (mobilization of more processing resources) for the delayed respect to the immediate retrieval conditionThis study was supported by grants from the Spanish Government, Ministerio de Ciencia e Innovación (PSI2014-55316-C3-3-R; PSI2017-89389-C2-2-R), with FEDER Funds; the Galician Government, Consellería de Cultura, Educación e Ordenación Universitaria, Axudas para a Consolidación e Estruturación de Unidades de Investigación Competitivas do Sistema Universitario de Galicia: GRC (GI-1807-USC); Ref: ED431-2017/27, with FEDER fundsS

    Brain atrophy and clinical characterization of adults with mild cognitive impairment and different cerebrospinal fluid biomarker profiles according to the AT(N) research framework of Alzheimer’s disease

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    Introduction: This study aimed to evaluate, in adults with mild cognitive impairment (MCI), the brain atrophy that may distinguish between three AT(N) biomarker-based profiles, and to determine its clinical value. Methods: Structural MRI (sMRI) was employed to evaluate the volume and cortical thickness differences in MCI patients with different AT(N) profiles, namely, A−T−(N)−: normal AD biomarkers; A+T−(N)−: AD pathologic change; and A+T+(N)+: prodromal AD. Sensitivity and specificity of these changes were also estimated. Results: An initial atrophy in medial temporal lobe (MTL) areas was found in the A+T−(N)− and A+T+(N)+ groups, spreading toward the parietal and frontal regions in A+T+(N)+ patients. These structural changes allowed distinguishing AT(N) profiles within the AD continuum; however, the profiles and their pattern of neurodegeneration were unsuccessful to determine the current clinical status. Conclusion: sMRI is useful in the determination of the specific brain structural changes of AT(N) profiles along the AD continuum, allowing differentiation between MCI adults with or without pathological AD biomarkersThis study was supported by grants from the Spanish Government, Ministerio de Ciencia e Innovación (PSI2017- 89389-C2-R and PID2020-114521RB-C21/C22); the Galician Government, Axudas para a Consolidación e Estruturación de Unidades de Investigación Competitivas do Sistema Universitario de Galicia: GRC (GI-1807- USC); Refs: ED431-2017/27 and ED431C-2021/04; all with ERDF/FEDER fundsS

    Increased risk of MAFLD and liver fibrosis in inflammatory bowel disease independent of classic metabolic risk factors

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    ackground & Aims There is conflicting evidence regarding the prevalence of and risk factors for metabolic-associated fatty liver disease (MAFLD) in patients with inflammatory bowel disease (IBD). We aimed to determine MAFLD prevalence and risk factors in IBD patients. Methods Cross-sectional, case-control study included all consecutive IBD patients treated at 2 different university hospitals. Controls were subjects randomly selected from the general population and matched by age, sex, type 2 diabetes status, and body mass index in a 1:2 ratio. MAFLD was confirmed by controlled attenuation parameter. Liver biopsies were collected when MAFLD with significant liver fibrosis was suspected. In addition, age- and fibrosis stage-paired non-IBD patients with biopsy-proven MAFLD served as a secondary control group. Results Eight hundred thirty-one IBD patients and 1718 controls were included. The prevalence of MAFLD and advanced liver fibrosis (transient elastography ≥9.7 kPa) was 42.00% and 9.50%, respectively, in IBD patients and 32.77% and 2.31%, respectively, in the general population (P < .001). A diagnosis of IBD was an independent predictor of MAFLD (adjusted odds ratio, 1.99; P < .001) and an independent risk factor for advanced liver fibrosis (adjusted odds ratio, 5.55; P < .001). Liver biopsies were obtained from 40 IBD patients; MAFLD was confirmed in all cases, and fibrosis of any degree was confirmed in 25 of 40 cases (62.5%). Body mass index and type 2 diabetes prevalence were significantly lower in IBD-MAFLD patients than in severity-paired patients with biopsy-proven MAFLD. Conclusions MAFLD and liver fibrosis are particularly prevalent in IBD patients, regardless of the influence of classic metabolic risk factors.Acknowledgements: The authors report funding support from the Spanish Instituto de Salud Carlos III-FEDER Grant (FIS - PI18/01304) related to this manuscript

    APPEAL-2: A pan-European qualitative study to explore the burden of peanut-allergic children, teenagers and their caregivers

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    Background: Allergy to Peanuts ImPacting Emotions And Life (APPEAL-1) was a recent European multi-country questionnaire survey that highlighted the negative impacts of peanut allergy (PA) on quality of life. A follow-on qualitative study, APPEAL-2, further assessed the burden of PA and associated coping strategies through semi-structured interviews. Objective: To gain qualitative insight on the strategies used to cope with and manage PA and the impact of these strategies on the quality of life of children, teenagers and caregivers. Methods: This cross-sectional qualitative study was conducted in eight European countries: the United Kingdom, France, Germany, Ireland, Spain, Italy, Denmark and the Netherlands. Semi-structured interviews were conducted with children (aged 8-12 years) and teenagers (aged 13-17 years) with self-/proxy-reported moderate or severe PA and with parents/caregivers of children or teenagers (aged 4-17 years) with moderate or severe PA. Data were analysed using thematic analysis; data saturation was assessed. Two conceptual models were developed to illustrate the impacts of PA and coping strategies used to manage them for (a) individuals with PA and (b) parents/caregivers of children with PA. Results: 107 participants were interviewed: 24 children, 39 teenagers and 44 caregivers. The conceptual models illustrated themes related to coping and control, driven by the fear of PA reactions, and the associated emotional, social, relationship and work impacts. Factors moderating these impacts included social attitudes and support, child-caregiver relationship and coping strategies used. Conclusions and Clinical Relevance: The APPEAL-2 results substantiate the findings of APPEAL-1; the results also suggest that the severity of experience with PA may not correlate with perception of its overall burden and show variable impacts by country

    Late-onset thymidine kinase 2 deficiency: a review of 18 cases

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    Background: TK2 gene encodes for mitochondrial thymidine kinase, which phosphorylates the pyrimidine nucleosides thymidine and deoxycytidine. Recessive mutations in the TK2 gene are responsible for the ‘myopathic form’ of the mitochondrial depletion/multiple deletions syndrome, with a wide spectrum of severity. Methods: We describe 18 patients with mitochondrial myopathy due to mutations in the TK2 gene with absence of clinical symptoms until the age of 12. Results: The mean age of onset was 31 years. The first symptom was muscle limb weakness in 10/18, eyelid ptosis in 6/18, and respiratory insufficiency in 2/18. All patients developed variable muscle weakness during the evolution of the disease. Half of patients presented difficulty in swallowing. All patients showed evidence of respiratory muscle weakness, with need for non-invasive Mechanical Ventilation in 12/18. Four patients had deceased, all of them due to respiratory insufficiency. We identified common radiological features in muscle magnetic resonance, where the most severely affected muscles were the gluteus maximus, semitendinosus and sartorius. On muscle biopsies typical signs of mitochondrial dysfunction were associated with dystrophic changes. All mutations identified were previously reported, being the most frequent the in-frame deletion p.Lys202del. All cases showed multiple mtDNA deletions but mtDNA depletion was present only in two patients. Conclusions: The late-onset is the less frequent form of presentation of the TK2 deficiency and its natural history is not well known. Patients with late onset TK2 deficiency have a consistent and recognizable clinical phenotype and a poor prognosis, due to the high risk of early and progressive respiratory insufficiency

    APPEAL‐1: A pan-European survey of patient/caregiver perceptions of peanut allergy management

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    Background: Peanut allergy (PA) is associated with marked quality‐of‐life (QoL) impairment. However, data are lacking on the experience and impact of living with PA from the perspectives of persons with PA (PwPA) and their caregivers. A llergy to P eanuts imP acting E motions A nd L ife study 1 (APPEAL‐1) was a pan‐European survey investigating these perspectives. This first of two articles reports clinical characteristics of PwPA and PA management practices. Methods: APPEAL‐1 was a quantitative, online survey conducted in eight European countries, developed by eight representatives of patient advocacy groups and five healthcare professionals and researchers. Eligible participants included adults with PA and parents/caregivers of PwPA who responded by self‐report and provided proxy‐report for the PwPA under their care. Data were summarised using nonweighted descriptive statistics. Results: Of 1846 completed/analysed questionnaires, 528 were from adults with PA (self‐report); 437 by proxy for children with PA (34 aged 0‐3 years, 287 aged 4‐12 years, 116 aged 13‐17 years); 881 from parents/caregivers (self‐report). Of PwPA (N=965), 95% reported diagnosis by healthcare professionals, mostly by clinical history and peanut‐specific allergy testing. Rates of allergic rhinitis, asthma, and other food allergies in PwPA were 50%, 42%, and 79%, respectively. Only 31% of PwPA received HCP advice/support following their worst allergic reaction, and 28% had not been prescribed an adrenaline auto‐injector. Results were similar by country but varied by age group. Conclusions: The APPEAL‐1 findings contribute to greater understanding of PA impact on PwPA, caregivers, and family members and the need for improved PA management across Europe

    Steppes, savannahs, forests and phytodiversity reservoirs during the Pleistocene in the Iberian Peninsula

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    A palaeobotanical analysis of the Pleistocene floras and vegetation in the Iberian Peninsula shows the existence of patched landscapes with Pinus woodlands, deciduous and mixed forests, parklands (savannah-like), shrublands, steppes and grasslands. Extinctions of Arctotertiary woody taxa are recorded during the Early and Middle Pleistocene, but glacial refugia facilitated the survival of a number of temperate, Mediterranean and Ibero-North African woody angiosperms. The responses of Iberian vegetation to climatic changes during the Pleistocene have been spatially and temporarily complex, including rapid changes of vegetation in parallel to orbital and suborbital variability, and situations of multi-centennial resilience or accommodation to climatic changes. Regional characteristics emerged as soon as for the Middle Pleistocene, if not earlier: Ericaceae in the Atlantic coast indicating wetter climate, thermo-mediterranean elements in the south as currently, and broad-leaf trees in the northeastern. Overall, steppe landscapes and open Pinus woodlands prevailed over many continental regions during the cold spells of the Late Pleistocene. The maintenance of a high phytodiversity during the glacials was linked to several refuge zones in the coastal shelves of the Mediterranean and intramountainous valleys. Northern Iberia, especially on coastal areas, was also patched with populations of tree species, and this is not only documented by palaeobotanical data (pollen, charcoal) but also postulated by phylogeographical models
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