Previous studies have indicated the potential of cerebrospinal fluid (CSF) α‐synuclein (α‐syn) to be an additional biomarker for improving differential diagnosis of Alzheimer’s disease (AD). We ...evaluated α‐syn diagnostic performance across a well‐characterized patient cohort with long‐term follow‐up. For this purpose, CSF α‐syn levels were determined in 25 subjects diagnosed with stable mild cognitive impairment (stable MCI; n = 25), 27 MCI cases due to AD (MCI‐AD; n = 32), 24 MCI cases due to Lewy body disease (MCI‐LBD; n = 24) and control subjects (Ctrl; n = 18). CSF α‐syn levels discriminate between the four groups. There were higher α‐syn levels in MCI‐AD patients and lower levels in MCI‐LBD patients. The combination of α‐syn and P‐tau resulted in a specificity of 99% and a sensitivity of 97% for MCI‐AD. MCI‐AD patients with early psychotic symptoms (n = 9) displayed a trend towards a decrease in P‐tau and α‐syn compared to the MCI‐AD patients without psychotic symptoms (n = 23). We conclude that adding CSF α‐syn to central core AD biomarkers improves an early differential diagnosis of MCI‐AD from other forms of MCI.
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Previous studies suggest the potential of α‐synuclein (α‐syn) as a cerebrospinal fluid (CSF) biomarker for Alzheimer’s disease (AD). We aim to study the potential of CSF α‐syn for improving differential diagnosis of AD in the earliest period of clinical symptoms, at the stage of clinical mild cognitive impairment (MCI) diagnosis. Our findings indicate that CSF α‐syn improves the differential diagnosis of MCI cases due to AD compared to MCI due to Lewy body disease, but also with stable MCI patients and non‐disease control subjects. The combination of α‐syn and P‐tau resulted in specificity and sensitivity ≥ 97% for MCI‐AD.
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Precipitation is a key climate parameter of vegetation and ecosystems in the Iberian Peninsula. Here, we use a regional pollen–climate calibration model and fossil pollen data from eight sites from ...the Atlantic coast to southern Spain to provide quantitative reconstructions of annual precipitation trends and excursions and their regional patterns for the last 11 700 years. The Early Holocene (11 700 to 11 000 cal. a BP) was characterized by high precipitation values followed by a slowly declining trend until about 9000 cal. a BP in the south and about 8000 cal. a BP in the north. From 8000 to 6000 cal. a BP the reconstructed precipitation values are the highest in most records, especially in those located in the Mediterranean climatic region in the southern part of the peninsula, with maximum values nearly 100% higher than the modern reconstructed values. The results suggest a declining precipitation during the Late Holocene in the south, with a positive excursion at around 2500 cal. a BP, while in the north precipitation remained high until 500 cal. a BP. However, the Late Holocene climate reconstructions in the Iberian Peninsula are biased by intensifying human impact on vegetation. The statistical time series analyses using SiZer technique do not indicate any statistically significant high‐frequency drought events in the region. In general, our results suggest regional differences in the precipitation patterns between the northern and southern parts of the peninsula, with a more distinct Middle Holocene period of high humidity in the south.
Understanding molecular mechanisms that control photosynthesis and water use efficiency in response to drought is crucial for plant species from dry areas. This study aimed to identify QTL for these ...traits in a Mediterranean conifer and tested their stability under drought.
High density linkage maps for Pinus pinaster were used in the detection of QTL for photosynthesis and water use efficiency at three water irrigation regimes. A total of 28 significant and 27 suggestive QTL were found. QTL detected for photochemical traits accounted for the higher percentage of phenotypic variance. Functional annotation of genes within the QTL suggested 58 candidate genes for the analyzed traits. Allele association analysis in selected candidate genes showed three SNPs located in a MYB transcription factor that were significantly associated with efficiency of energy capture by open PSII reaction centers and specific leaf area.
The integration of QTL mapping of functional traits, genome annotation and allele association yielded several candidate genes involved with molecular control of photosynthesis and water use efficiency in response to drought in a conifer species. The results obtained highlight the importance of maintaining the integrity of the photochemical machinery in P. pinaster drought response.
In this paper we present a review of the available Holocene pollen records from the Spanish Central System (113 sites and 150 14C dates). Palynological data obtained from pollen analyses of ...peat-bogs, lakes and archaeological sites, as well as radiocarbon dating, were used to infer the human impact on vegetation and landscape during the last 9 millennia. The Neolithic contribution to the configuration of landscape is scarce, limited to the valleys, while Chalcolithic settlements and their related activities (agriculture and grazing) represent the first evidence of significant human impact on the high-mountains. The pollen record has allowed us to relate two cultural periods of changing, the Copper Age–Early Bronze Age and Late Bronze Age–Early Iron Age transitions, to abrupt climate disruptions, the so-called 4.2 and 2.8 ka cal BP events respectively. From the Iron Age to the Early Middle Ages, anthropic activities were still sporadic, mainly located in the lowlands, but from the Feudal Period onwards, when La Mesta transhumance system takes place, high-mountain landscapes changed dramatically. Late Modern Period brings a further intensification of human pressure, especially related to forestry, with widespread pinewood afforestation.
Alzheimer's disease (AD) accompanied by psychotic symptoms (PS) has a poor prognosis and may be associated with imbalances in key neural proteins such as alpha-synuclein (AS).
The aim of the study ...was to evaluate the diagnostic validity of AS levels in the cerebrospinal fluid (CSF) as a predictor of the emergence of PS in patients with prodromal AD.
Patients with mild cognitive impairment were recruited between 2010 and 2018. Core AD biomarkers and AS levels were measured in CSF obtained during the prodromal phase of the illness. All patients who met the NIA-AA 2018 criteria for AD biomarkers received treatment with anticholinesterasic drugs. Follow-up evaluations were conducted to assess patients for the presence of psychosis using current criteria; the use of neuroleptic drugs was required for inclusion in the psychosis group. Several comparisons were made, taking into account the timing of the emergence of PS.
A total of 130 patients with prodromal AD were included in this study. Of these, 50 (38.4%) met the criteria for PS within an 8-year follow-up period. AS was found to be a valuable CSF biomarker to differentiate between the psychotic and non-psychotic groups in every comparison made, depending on the onset of PS. Using an AS level of 1,257 pg/mL as the cutoff, this predictor achieved at least 80% sensitivity.
To our knowledge, this study represents the first time that a CSF biomarker has shown diagnostic validity for prediction of the emergence of PS in patients with prodromal AD.
Patients with systemic sclerosis (SSc) are at increased risk of cancer, a growing cause of non–SSc-related death among these patients. We analyzed the increased cancer risk among Spanish patients ...with SSc using standardized incidence ratios (SIRs) and identified independent cancer risk factors in this population.
Spanish Scleroderma Registry data were analyzed to determine the demographic characteristics of patients with SSc, and logistic regression was used to identify cancer risk factors. SIRs with 95% confidence intervals (CIs) relative to the general Spanish population were calculated.
Of 1930 patients with SSc, 206 had cancer, most commonly breast, lung, hematological, and colorectal cancers. Patients with SSc had increased risks of overall cancer (SIR 1.48, 95% CI 1.36–1.60; P < 0.001), and of lung (SIR 2.22, 95% CI 1.77–2.73; P < 0.001), breast (SIR 1.31, 95% CI 1.10–1.54; P = 0.003), and hematological (SIR 2.03, 95% CI 1.52–2.62; P < 0.001) cancers. Cancer was associated with older age at SSc onset (odds ratio OR 1.22, 95% CI 1.01–1.03; P < 0.001), the presence of primary biliary cholangitis (OR 2.35, 95% CI 1.18–4.68; P = 0.015) and forced vital capacity <70% (OR 1.8, 95% CI 1.24–2.70; P = 0.002). The presence of anticentromere antibodies lowered the risk of cancer (OR 0.66, 95% CI 0.45–0.97; P = 0.036).
Spanish patients with SSc had an increased cancer risk compared with the general population. Some characteristics, including specific autoantibodies, may be related to this increased risk.
•Systemic sclerosis patients have increased risk of lung, breast, and blood cancer.•Primary biliary cholangitis is linked to a 6-fold greater risk of breast cancer.•Moderate or severe interstitial lung disease is linked to a higher risk of cancer.•Anti-centromere antibodies are associated with a lower risk of cancer.
Optical coherence tomography (OCT) and OCT angiography (OCTA) have been a technological breakthrough in the diagnosis, treatment, and follow-up of many retinal diseases, thanks to its resolution and ...its ability to inform of the retinal state in seconds, which gives relevant information about retinal degeneration.
In this review, we present an immunohistochemical description of the human and mice retina and we correlate it with the OCT bands in health and pathological conditions. Here, we propose an interpretation of the four outer hyperreflective OCT bands with a correspondence to retinal histology: the first and innermost band as the external limiting membrane (ELM), the second band as the cone ellipsoid zone (EZ), the third band as the outer segment tips phagocytosed by the pigment epithelium (PhaZ), and the fourth band as the mitochondria in the basal portion of the RPE (RPEmitZ). The integrity of these bands would reflect the health of photoreceptors and retinal pigment epithelium.
Moreover, we describe how the vascular plexuses vary in different regions of the healthy human and mice retina, using OCTA and immunohistochemistry. In humans, four, three, two or one plexuses can be observed depending on the distance from the fovea. Also, specific structures such as vascular loops in the intermediate capillary plexus, or spider-like structures of interconnected capillaries in the deep capillary plexus are found. In mice, three vascular plexuses occupy the whole retina, except in the most peripheral retina where only two plexuses are found. These morphological issues should be considered when assessing a pathology, as some retinal diseases are associated with structural changes in blood vessels.
Therefore, the analysis of OCT bands and OCTA vascular plexuses may be complementary for the diagnosis and prognosis of retinal degenerative processes, useful to assess therapeutic approaches, and it is usually correlated to visual acuity.
High-mountain peatlands are essential ecosystems for habitats, biodiversity, water, and carbon cycling, butthere is little comprehensive information in central Iberia. We present results of research ...concerning the distribution,geormorphology, floristic, geobotany, and habitat diversity of peatlands in the Gredos Regional Park (Iberian Central System).We identified 72 peatlands covering 117 ha and ranging in size from 0.01 to 17.34 ha. Peatlands occur primarily in theupper orosubmediterranean bioclimatic belt at 1775–2230 m asl. From a geomorphological point of view, 9 differentpeatland typologies have been defined. Multivariate analyses (agglomerative cluster analysis and principal componentanalysis) of 103 relevés allowed us to classify the sampled peatland stands into 7 plant communities and 4 Europeanhabitats that formed along complex hydrogeomorphic conditions, and to propose a new subassociation of other communitypreviously described (Caricetum echinato-nigrae lycopodielletosum inundatae). The main threat to Gredenseanpeatlands is pastoral pressure, which affects 15 of them intensively, mainly between the upper supramediterranean andthe lower orosubmediterranean bioclimatic belts (~1314–1700 m asl). Seven bryophytes and three vascular plantsdocumented in the Gredos Regional Park peatlands are included in the IUCN Red List. From the point of view ofconservation priority, the most threatened correspond to transition mires communities (Habitat 7140) growing inoligotrophic and minerotrophic peatlands (Caricion nigrae vegetation). Particularly, the Iberian Central System endemicSedo lagascae-Eriophoretum latifolii association is the one that has achieved the highest score in the five criteriaconsidered in this regard because Meesia triquetra, a species with the category of “critically endangered”, inhabits it.
There is a wealth of studies dealing with the reconstruction of past environmental changes and their effects on vegetation composition in NW Iberia, but none of them have focused specifically on the ...post-disturbance dynamics (i.e. the type of response) of the vegetation at different space and time scales. To fill this gap, we analysed the record of pollen and non-pollen palynomorphs (NPP) of a 235-cm thick colluvial sequence spanning the last ~13,900years. The aims were to detect the changes in vegetation, identify the responsible drivers and determine the type of responses to disturbance. To extract this information we applied multivariate statistical techniques (constrained cluster analysis and principal components analysis on transposed matrices, PCAtr) to the local (hydro-hygrophytes and NPP) and regional (land pollen) datasets separately. In both cases the cluster analysis resulted in eight local and regional assemblage zones, while five (local types) and four (regional types) principal components were obtained by PCAtr to explain 94.1% and 96.6% of the total variance, respectively. The main drivers identified were climate change, grazing pressure, fire events and cultivation. The vegetation showed gradual, threshold and elastic responses to these drivers, at different space (local vs. regional) and time scales, revealing a complex ecological history. Regional responses to perturbations were sometimes delayed with respect to the local response. The results also showed an ecosystem resilience, such as the persistence of open Betula-dominated vegetation community for ~1700years after the onset of the Holocene, and elastic responses, such as the oak woodland to the 8200calyr BP dry/cold event. Our results support the notion that palaeoecological research is a valuable tool to investigate ecosystem history, their responses to perturbations and their ability to buffer them. This knowledge is critical for modelling the impact of future environmental change and to help to manage the landscape more sustainably.
► Palynological study of a colluvial sequence from NW Spain spanning the last 13,900yr ► Aiming to detect vegetation change, driving factors and post-disturbance responses ► Multivariate statistics were applied: constrain cluster and PCA (transposed matrix). ► Vegetation showed varied responses at different space and time scales. ► Palaeoecology is a tool to assess system responses to environmental perturbations.
En esta investigación hemos querido indagar en las posibilidades que tienen los sistemas de inteligencia artificial de ser utilizados en el ámbito judicial en España, aunque bien podríamos extrapolar ...nuestras conclusiones a cualquier otro Estado de Derecho europeo. Sabemos que en Estados Unidos y en el mundo anglosajón en general el uso de estos sistemas está prácticamente liberalizado, pero el proyecto de Reglamento sobre IA de la Unión Europea y el proyecto de Convenio Marco sobre IA del Consejo de Europa imponen límites a la proporcionalidad y el respeto de los derechos fundamentales que son ciertamente necesarios para no socavar las garantías procesales. Los órdenes jurisdiccionales más adecuados para el uso de la IA son el penal y el civil, ya que el contencioso-administrativo, con sus potestades discrecionales, sus conceptos jurídicos indeterminados y la existencia de intereses generales lo hacen inadecuado. Sin embargo, hemos propuesto algunos usos posibles en este proceso.
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