Publications by authors named "Joana Pereira"

238 Publications

Plasma GFAP is an early marker of amyloid-β but not tau pathology in Alzheimer's disease.

Brain 2021 Jul 14. Epub 2021 Jul 14.

Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Sweden.

Although recent clinical trials targeting amyloid-β (Aβ) in Alzheimer's disease (AD) have shown promising results, there is increasing evidence suggesting that understanding alternative disease pathways that interact with Aβ metabolism and amyloid pathology might be important to halt the clinical deterioration. In particular, there is evidence supporting a critical role of astroglial activation and astrocytosis in AD. However, to this date, no studies have assessed whether astrocytosis is independently related to either Aβ or tau pathology, respectively, in vivo. To address this question, we determined the levels of the astrocytic marker glial fibrillary acidic protein (GFAP) in plasma and cerebrospinal fluid (CSF) of 217 Aβ-negative cognitively unimpaired individuals, 71 Aβ-positive cognitively unimpaired individuals, 78 Aβ-positive cognitively impaired individuals, 63 Aβ-negative cognitively impaired individuals and 75 patients with a non-AD neurodegenerative disorder from the Swedish BioFINDER-2 study. Subjects underwent longitudinal Aβ (18F-flutemetamol) and tau (18F-RO948) positron emission tomography (PET) as well as cognitive testing. We found that plasma GFAP concentration was significantly increased in all Aβ-positive groups compared with subjects without Aβ pathology (p < 0.01). In addition, there were significant associations between plasma GFAP with higher Aβ-PET signal in all Aβ-positive groups, but also in cognitively normal individuals with normal Aβ values (p < 0.001), which remained significant after controlling for tau-PET signal. Furthermore, plasma GFAP could predict Aβ-PET positivity with an area under the curve of 0.76, which was greater than the performance achieved by CSF GFAP (0.69) and other glial markers (CSF YKL-40: 0.64, sTREM2: 0.71). Although correlations were also observed between tau-PET and plasma GFAP, these were no longer significant after controlling for Aβ-PET. In contrast to plasma GFAP, CSF GFAP concentration was significantly increased in non-AD patients compared to other groups (p < 0.05) and correlated with Aβ-PET only in Aβ-positive cognitively impaired individuals (p = 0.005). Finally, plasma GFAP was associated with both longitudinal Aβ-PET and cognitive decline, and mediated the effect of Aβ-PET on tau-PET burden, suggesting that astrocytosis secondary to Aβ aggregation might promote tau accumulation. Altogether, these findings indicate that plasma GFAP is an early marker associated with brain Aβ pathology but not tau aggregation, even in cognitively normal individuals with a normal Aβ status. This suggests that plasma GFAP should be incorporated in current hypothetical models of AD pathogenesis and be used as a non-invasive and accessible tool to detect early astrocytosis secondary to Aβ pathology.
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http://dx.doi.org/10.1093/brain/awab223DOI Listing
July 2021

Probability of Transition to Psychosis in Individuals at Clinical High Risk: An Updated Meta-analysis.

JAMA Psychiatry 2021 Jul 14. Epub 2021 Jul 14.

Early Psychosis: Interventions and Clinical-detection (EPIC) Lab, Institute of Psychiatry, Psychology & Neuroscience, Department of Psychosis Studies, King's College London, London, United Kingdom.

Importance: Estimating the current likelihood of transitioning from a clinical high risk for psychosis (CHR-P) to psychosis holds paramount importance for preventive care and applied research.

Objective: To quantitatively examine the consistency and magnitude of transition risk to psychosis in individuals at CHR-P.

Data Sources: PubMed and Web of Science databases until November 1, 2020. Manual search of references from previous articles.

Study Selection: Longitudinal studies reporting transition risks in individuals at CHR-P.

Data Extraction And Synthesis: Meta-analysis compliant with Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guidelines; independent data extraction, manually and through digitalization of Kaplan-Meier curves.

Main Outcome And Measures: Primary effect size was cumulative risk of transition to psychosis at 0.5, 1, 1.5, 2, 2.5, 3, 4, and more than 4 years' follow-up, estimated using the numbers of individuals at CHR-P transitioning to psychosis at each time point. These analyses were complemented by meta-analytical Kaplan-Meier curves and speed of transition to psychosis (hazard rate). Random-effects meta-analysis, between-study heterogeneity analysis, study quality assessment, and meta-regressions were conducted.

Results: A total of 130 studies and 9222 individuals at CHR-P were included. The mean (SD) age was 20.3 (4.4) years, and 5100 individuals (55.3%) were male. The cumulative transition risk was 0.09 (95% CI, 0.07-0.10; k = 37; n = 6485) at 0.5 years, 0.15 (95% CI, 0.13-0.16; k = 53; n = 7907) at 1 year, 0.20 (95% CI, 0.17-0.22; k = 30; n = 5488) at 1.5 years, 0.19 (95% CI, 0.17-0.22; k = 44; n = 7351) at 2 years, 0.25 (95% CI, 0.21-0.29; k = 19; n = 3114) at 2.5 years, 0.25 (95% CI, 0.22-0.29; k = 29; n = 4029) at 3 years, 0.27 (95% CI, 0.23-0.30; k = 16; n = 2926) at 4 years, and 0.28 (95% CI, 0.20-0.37; k = 14; n = 2301) at more than 4 years. The cumulative Kaplan-Meier transition risk was 0.08 (95% CI, 0.08-0.09; n = 4860) at 0.5 years, 0.14 (95% CI, 0.13-0.15; n = 3408) at 1 year, 0.17 (95% CI, 0.16-0.19; n = 2892) at 1.5 years, 0.20 (95% CI, 0.19-0.21; n = 2357) at 2 years, 0.25 (95% CI, 0.23-0.26; n = 1444) at 2.5 years, 0.27 (95% CI, 0.25-0.28; n = 1029) at 3 years, 0.28 (95% CI, 0.26-0.29; n = 808) at 3.5 years, 0.29 (95% CI, 0.27-0.30; n = 737) at 4 years, and 0.35 (95% CI, 0.32-0.38; n = 114) at 10 years. The hazard rate only plateaued at 4 years' follow-up. Meta-regressions showed that a lower proportion of female individuals (β = -0.02; 95% CI, -0.04 to -0.01) and a higher proportion of brief limited intermittent psychotic symptoms (β = 0.02; 95% CI, 0.01-0.03) were associated with an increase in transition risk. Heterogeneity across the studies was high (I2 range, 77.91% to 95.73%).

Conclusions And Relevance: In this meta-analysis, 25% of individuals at CHR-P developed psychosis within 3 years. Transition risk continued increasing in the long term. Extended clinical monitoring and preventive care may be beneficial in this patient population.
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http://dx.doi.org/10.1001/jamapsychiatry.2021.0830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281006PMC
July 2021

High-accuracy protein structure prediction in CASP14.

Proteins 2021 Jul 3. Epub 2021 Jul 3.

Department of Protein Evolution, Max Planck Institute for Developmental Biology, Tübingen, Germany.

The application of state-of-the-art deep-learning approaches to the protein modeling problem has expanded the "high-accuracy" category in CASP14 to encompass all targets. Building on the metrics used for high-accuracy assessment in previous CASPs, we evaluated the performance of all groups that submitted models for at least 10 targets across all difficulty classes, and judged the usefulness of those produced by AlphaFold2 (AF2) as molecular replacement search models with AMPLE. Driven by the qualitative diversity of the targets submitted to CASP, we also introduce DipDiff as a new measure for the improvement in backbone geometry provided by a model versus available templates. Although a large leap in high-accuracy is seen due to AF2, the second-best method in CASP14 out-performed the best in CASP13, illustrating the role of community-based benchmarking in the development and evolution of the protein structure prediction field.
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http://dx.doi.org/10.1002/prot.26171DOI Listing
July 2021

Vital Pulp Therapy in Permanent Mature Posterior Teeth with Symptomatic Irreversible Pulpitis: A Systematic Review of Treatment Outcomes.

Medicina (Kaunas) 2021 Jun 3;57(6). Epub 2021 Jun 3.

MSc Endodontics Program, Faculty of Dentistry, University of Toronto, Toronto, ON M5G 1G6, Canada.

: Symptomatic irreversible pulpitis in permanent mature teeth is a common indication for nonsurgical root canal treatment (NSRCT), but contemporary studies have reported on vital pulp therapy (VPT) applied in such teeth as a less invasive treatment. This systematic review assessed the outcomes of VPT, including partial and full pulpotomy performed with hydraulic calcium silicate cements (HCSCs) in permanent mature posterior teeth diagnosed with symptomatic irreversible pulpitis. : The PRISMA guidelines were followed. The search strategy included PubMed, EMBASE, Cochrane library and grey literature electronic databases. The quality assessment of the identified studies followed the Cochrane Collaboration Risk of Bias, ROBINS-I and Newcastle-Ottawa Scale tools. : The search of primary databases identified 142 articles, of which 9 randomized controlled trials and 3 prospective cohort studies were selected for review. The risk-of-bias was assessed as 'high' or 'serious', 'fair', and 'low' for three, seven and two articles, respectively. One to five years after VPT using HCSCs, the success rates mostly ranged from 78 to 90%. Based on two articles, the outcomes of the VPT and NSRCT were comparable at one and five years. Despite the necessity for the intra-operative pulp assessment in VPT procedures, the majority of the studies did not fully report on this step or on the time needed to achieve hemostasis. Small sample sizes, of under 23 teeth, were reported in three studies. : The reviewed 12 articles reported favorable outcomes of the VPT performed with HCSCs in permanent mature posterior teeth with symptomatic irreversible pulpitis, with radiographic success in the range of 81 to 90%. Two articles suggested comparable outcomes of the VPT and root canal treatment. Universal case selection and outcome criteria needs to be established for VPT when considered as an alternative to NSRCT. This evidence supports the need for further research comparing longer-term outcomes of both of the treatment modalities.
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http://dx.doi.org/10.3390/medicina57060573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8228104PMC
June 2021

Longitudinal outcome of attenuated positive symptoms, negative symptoms, functioning and remission in people at clinical high risk for psychosis: a meta-analysis.

EClinicalMedicine 2021 Jun 16;36:100909. Epub 2021 Jun 16.

Early Psychosis: Interventions and Clinical-detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK.

Background: Little is known about clinical outcomes other than transition to psychosis in people at Clinical High-Risk for psychosis (CHR-P). Our aim was to comprehensively meta-analytically evaluate for the first time a wide range of clinical and functional outcomes beyond transition to psychosis in CHR-P individuals.

Methods: PubMed and Web of Science were searched until November 2020 in this PRISMA compliant meta-analysis (PROSPERO:CRD42020206271). Individual longitudinal studies conducted in individuals at CHR-P providing data on at least one of our outcomes of interest were included. We carried out random-effects pairwise meta-analyses, meta-regressions, and assessed publication bias and study quality. Analyses were two-tailed with α=0.05.

Findings: 75 prospective studies were included (n=5,288, age=20.0 years, females=44.5%). Attenuated positive symptoms improved at 12 (Hedges' g=0.753, 95%CI=0.495-1.012) and 24 (Hedges' g=0.836, 95%CI=0.463-1.209), but not ≥36 months (Hedges' g=0.315. 95%CI=-0.176-0.806). Negative symptoms improved at 12 (Hedges' g=0.496, 95%CI=0.315-0.678), but not 24 (Hedges' g=0.499, 95%CI=-0.137-1.134) or ≥36 months (Hedges' g=0.033, 95%CI=-0.439-0.505). Depressive symptoms improved at 12 (Hedges' g=0.611, 95%CI=0.441-0.782) and 24 (Hedges' g=0.583, 95%CI=0.364-0.803), but not ≥36 months (Hedges' g=0.512 95%CI=-0.337-1.361). Functioning improved at 12 (Hedges' g=0.711, 95%CI=0.488-0.934), 24 (Hedges' g=0.930, 95%CI=0.553-1.306) and ≥36 months (Hedges' g=0.392, 95%CI=0.117-0.667). Remission from CHR-P status occurred in 33.4% (95%CI=22.6-44.1%) at 12 months, 41.4% (95%CI=32.3-50.5%) at 24 months and 42.4% (95%CI=23.4-61.3%) at ≥36 months. Heterogeneity across the included studies was significant and ranged from I=53.6% to I=96.9%. The quality of the included studies (mean±SD) was 4.6±1.1 (range=2-8).

Interpretation: CHR-P individuals improve on symptomatic and functional outcomes over time, but these improvements are not maintained in the longer term, and less than half fully remit. Prolonged duration of care may be needed for this patient population to optimize outcomes.

Funding: None.
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http://dx.doi.org/10.1016/j.eclinm.2021.100909DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219991PMC
June 2021

Online detection of movement during natural and self-initiated reach-and-grasp actions from EEG signals.

J Neural Eng 2021 Jul 2;18(4). Epub 2021 Jul 2.

Institute of Neural Engineering, Graz University of Technology, Graz, Austria.

Movement intention detection using electroencephalography (EEG) is a challenging but essential component of brain-computer interfaces (BCIs) for people with motor disabilities.The goal of this study is to develop a new experimental paradigm to perform asynchronous online detection of movement based on low-frequency time-domain EEG features, concretely on movement-related cortical potentials. The paradigm must be easily transferable to people without any residual upper-limb movement function and the BCI must be independent of upper-limb movement onset measurements and external cues.. In a study with non-disabled participants, we evaluated a novel BCI paradigm to detect self-initiated reach-and-grasp movements. Two experimental conditions were involved. In one condition, participants performed reach-and-grasp movements to a target and simultaneously shifted their gaze towards it. In a control condition, participants solely shifted their gaze towards the target (oculomotor task). The participants freely decided when to initiate the tasks. After eye artefact correction, the EEG signals were time-locked to the saccade onset and the resulting amplitude features were exploited on a hierarchical classification approach to detect movement asynchronously.. With regards to BCI performance, 54.1% (14.4% SD) of the movements were correctly identified, and all participants achieved a performance above chance-level (around 12%). An average of 21.5% (14.1% SD) of the oculomotor tasks were falsely detected as upper-limb movement. In an additional rest condition, 1.7 (1.6 SD) false positives per minute were measured. Through source imaging, movement information was mapped to sensorimotor, posterior parietal and occipital areas.. We present a novel approach for movement detection using EEG signals which does not rely on upper-limb movement onset measurements or on the presentation of external cues. The participants' behaviour closely matches the natural behaviour during goal-directed reach-and-grasp movements, which also constitutes an advantage with respect to current BCI protocols.
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http://dx.doi.org/10.1088/1741-2552/ac0b52DOI Listing
July 2021

Dendritic spines are lost in clusters in Alzheimer's disease.

Sci Rep 2021 Jun 11;11(1):12350. Epub 2021 Jun 11.

Laboratorio Cajal de Circuitos Corticales (CTB), Centro de Tecnología Biomédica, Universidad Politécnica de Madrid, Campus Montegancedo S/N, Pozuelo de Alarcon, 28223, Madrid, Spain.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by a deterioration of neuronal connectivity. The pathological accumulation of tau in neurons is one of the hallmarks of AD and has been connected to the loss of dendritic spines of pyramidal cells, which are the major targets of cortical excitatory synapses and key elements in memory storage. However, the detailed mechanisms underlying the loss of dendritic spines in individuals with AD are still unclear. Here, we used graph-theory approaches to compare the distribution of dendritic spines from neurons with and without tau pathology of AD individuals. We found that the presence of tau pathology determines the loss of dendritic spines in clusters, ruling out alternative models where spine loss occurs at random locations. Since memory storage has been associated with synaptic clusters, the present results provide a new insight into the mechanisms by which tau drives synaptic damage in AD, paving the way to memory deficits through alterations of spine organization.
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http://dx.doi.org/10.1038/s41598-021-91726-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196005PMC
June 2021

Sex differences in off-target binding using tau positron emission tomography.

Neuroimage Clin 2021 May 29;31:102708. Epub 2021 May 29.

Clinical Memory Research Unit, Department of Clinical Sciences, Malmö, Lund University, Sweden; Memory Clinic, Skåne University Hospital, Malmö, Sweden.

Purpose: Off-target binding in the skull and meninges is observed in some subjects undergoing tau positron emission tomography (PET) and could potentially differ between men and women. In this study we elucidate sex differences in tau off-target binding using three different tau PET tracers.

Methods: 541 cognitively unimpaired amyloid-β negative participants underwent tau PET using [F]flortaucipir (n = 165), [F]RO948 (n = 189) and [F]MK6240 (n = 187). Baseline SUVR-values were compared between females and males at the voxel level and using a region-of-interest (ROI) encompassing the skull/meninges. In addition, we assessed the cross-sectional relationship between baseline skull/meninges SUVR and age and assessed change in skull/meningeal SUVR values over time in a subsample with longitudinal data (n = 63).

Results: Voxel-wise analysis showed higher meningeal off-target binding in women compared to men across all three tracers. The SUVRs in the skull/meningeal ROI were highest using [F]RO948, followed by [F]MK6240 and [F]flortaucipir (p < 0.001). For all tracers, females showed higher skull/meningeal ROI retention (mean SUVR ± SD [F]flortaucipir: 0.82 ± 0.14; [F]RO948: 1.26 ± 0.30; [F]MK6240: 1.09 ± 0.19) compared to men ([F]flortaucipir: 0.70 ± 0.11; [F]RO948: 1.10 ± 0.24; [F]MK6240: 0.97 ± 0.17) (p < 0.001). For [F]flortaucipir and [F]RO948, off-target binding in the skull/meninges decreased with age.

Conclusion: There is an effect of sex on off-target retention in the meninges/skull across [F]flortaucipir, [F]RO948, and [F]MK6240 tau PET tracers.
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http://dx.doi.org/10.1016/j.nicl.2021.102708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182304PMC
May 2021

Plasma markers predict changes in amyloid, tau, atrophy and cognition in non-demented subjects.

Brain 2021 Jun 2. Epub 2021 Jun 2.

Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, SE-20502 Malmö, Sweden.

It is currently unclear whether plasma biomarkers can be used as independent prognostic tools to predict changes associated with early Alzheimer's disease (AD). In this study we sought to address this question by assessing whether plasma biomarkers can predict changes in amyloid load, tau accumulation, brain atrophy and cognition in non-demented individuals. To achieve this, plasma amyloid-β 42/40 (Aβ42/40), phosphorylated-tau181 (P-tau181), phosphorylated-tau217 (P-tau217) and neurofilament light (NfL) were determined in 159 non-demented individuals, 123 patients with AD dementia and 35 patients with a non-AD dementia from the Swedish BioFINDER-2 study, who underwent longitudinal amyloid (18 F-flutemetamol) and tau (18 F-RO948) positron emission tomography (PET), structural magnetic resonance imaging (T1-weighted) and cognitive testing. Our univariate linear mixed effect models showed there were several significant associations between the plasma biomarkers with imaging and cognitive measures. However, when all biomarkers were included in the same multivariate linear mixed effect models, we found that increased longitudinal amyloid-PET signals were independently predicted by low baseline plasma Aβ42/40 (p = 0.012), whereas increased tau-PET signals, brain atrophy and worse cognition were independently predicted by high plasma P-tau217 (p < 0.004). These biomarkers performed equally well or better than the corresponding biomarkers measured in the cerebrospinal fluid. In addition, they showed a similar performance to binary plasma biomarker values defined using the Youden index, which can be more easily implemented in the clinic. In addition, plasma Aβ42/40 and P-tau217 did not predict longitudinal changes in patients with a non-AD neurodegenerative disorder. In conclusion, our findings indicate that plasma Aβ42/40 and P-tau217 could be useful in clinical practice, research and drug development as prognostic markers of future AD pathology.
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http://dx.doi.org/10.1093/brain/awab163DOI Listing
June 2021

Ineffective Pregnancy Prevention During Adolescence: Assisting Healthcare Providers in Portugal With Individualized Risk Assessment.

J Prim Prev 2021 Aug 31;42(4):385-407. Epub 2021 May 31.

Center for Research in Neuropsychology and Cognitive Behavioral Intervention, Faculty of Psychology and Education Sciences, University of Coimbra, Rua Do Colégio Novo, 3000-115, Coimbra, Portugal.

In this study, we describe the relative contributions of and interactions between individual risk factors associated with ineffective pregnancy prevention among female adolescents in Portugal. Our sample consisted of 856 sexually experienced female adolescents (10-19 years) who did not intend to become pregnant. Of these, 379 were pregnant, and the residual (477) had never been pregnant. We used classification tree analysis to describe the interplay among a set of established sociodemographic, familial, reproductive, and relationship factors as predictors of ineffective pregnancy prevention. The tree model showed good predictive properties. Seven profiles predicted one-half to all the cases of ineffective pregnancy prevention. Ineffective pregnancy prevention was predicted by adolescents' grade level and different combinations of variables, specifically female age, age at the time of first sexual intercourse, religious beliefs, place of residence, maternal pregnancy before age 20, household structure in childhood, and partner's age difference. According to our findings, limiting assessments to the cumulative presence of risk factors may be insufficient to accurately identify adolescents at elevated risk of unwanted pregnancy, as the impact of any given risk factor may vary according to other factors. Our findings may contribute to the development of a risk assessment tool that may support healthcare providers' efforts to provide individualized risk assessment for adolescent patients and, thus, to better support pregnancy prevention.
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http://dx.doi.org/10.1007/s10935-021-00637-0DOI Listing
August 2021

The breakthrough in protein structure prediction.

Biochem J 2021 May;478(10):1885-1890

Department of Protein Evolution, Max Planck Institute for Developmental Biology, 72076 Tübingen, Germany.

Proteins are the essential agents of all living systems. Even though they are synthesized as linear chains of amino acids, they must assume specific three-dimensional structures in order to manifest their biological activity. These structures are fully specified in their amino acid sequences - and therefore in the nucleotide sequences of their genes. However, the relationship between sequence and structure, known as the protein folding problem, has remained elusive for half a century, despite sustained efforts. To measure progress on this problem, a series of doubly blind, biennial experiments called CASP (critical assessment of structure prediction) were established in 1994. We were part of the assessment team for the most recent CASP experiment, CASP14, where we witnessed an astonishing breakthrough by DeepMind, the leading artificial intelligence laboratory of Alphabet Inc. The models filed by DeepMind's structure prediction team using the program AlphaFold2 were often essentially indistinguishable from experimental structures, leading to a consensus in the community that the structure prediction problem for single protein chains has been solved. Here, we will review the path to CASP14, outline the method employed by AlphaFold2 to the extent revealed, and discuss the implications of this breakthrough for the life sciences.
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http://dx.doi.org/10.1042/BCJ20200963DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166336PMC
May 2021

Impacts of wildfires in aquatic organisms: biomarker responses and erythrocyte nuclear abnormalities in Gambusia holbrooki exposed in situ.

Environ Sci Pollut Res Int 2021 May 14. Epub 2021 May 14.

CESAM - Centre for Environmental and Marine Studies, University of Aveiro, Aveiro, Portugal.

Wildfires are an environmental concern due to the loss of forest area and biodiversity, but also because their role as drivers of freshwater systems contamination by metals. In this context, the fish Gambusia holbrooki was used as a model, deployed for in situ exposure in watercourses standing within a recently burnt area and further assessment of toxic effects. The fish were exposed during 4 days at four different sites: one upstream and another downstream the burnt area and two within the burnt area. Biochemical biomarkers for oxidative stress and damage were assessed. The extent of lipoperoxidative damage was monitored by quantifying malondialdehyde and DNA damage evaluated through erythrocyte nuclear abnormalities observation. Chemical analysis revealed higher metal levels within the burnt area, and exposed fish consistently showed pro-oxidative responses therein, particularly an increase of gill glutathione peroxidase and glutathione reductase activity, the records doubling compared to samples from sites in the unburnt area; also the activity of glutathione-S-transferases comparatively increased (by 2-fold in the liver) in samples from the burnt area, and malondialdehyde was produced twice as much therein and in samples downstream the burnt area reflecting oxidative damage. Consistently, the frequency of erythrocyte nuclear abnormalities was higher at sites within and downstream the burnt area. This study supports the use of sensitive oxidative stress and genotoxicity biomarkers for an early detection of potentially noxious ecological effects of wildfires runoff.
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http://dx.doi.org/10.1007/s11356-021-14377-5DOI Listing
May 2021

Sensitivity of a widespread groundwater copepod to different contaminants.

Chemosphere 2021 Jul 12;274:129911. Epub 2021 Feb 12.

Natural History Museum of Denmark, University of Copenhagen, Copenhagen, Denmark; Centre for Ecology, Evolution and Environmental Changes (cE3c), and Departamento de Biologia Animal, Faculdade de Ciências, Universidade de Lisboa, Lisbon, Portugal. Electronic address:

Groundwater is an indispensable resource for humankind and sustainable biomes functioning. Anthropogenic disturbance threatens groundwater ecosystems globally, but to which extent groundwater organisms respond to stressors remains poorly understood. Groundwater animals are rare, with small populations, difficult to find and to breed in the lab, which poses a main challenge to the assessment of their responses to pollutants. Despite the difficulties, assessing the toxicity of a large spectrum of stressors to groundwater organisms is a priority to inform towards appropriate environmental protection of these ecosystems. We tested the sensitivity to CuSO, diclofenac, and NaCl of a groundwater population of the copepod Diacyclops crassicaudis crassicaudis and compared its sensitivity with the model organism Daphnia magna. We ranked its sensitivity using a species sensitivity distribution (SSD) approach using the feasible data available for groundwater and surface crustaceans. Our results show that the most toxic compound was CuSO for which higher amount of data was recorded and wider variability in response was observed. It was followed by diclofenac, largely lacking data for groundwater-adapted organisms, and the least toxic compound was NaCl. The differential sensitivity between D. crassicaudis and D. magna was contaminant-dependent. As a general trend D. crassicaudis was always distributed in the upper part of the SSD curves together with other groundwater-adapted organisms. Our results highlight that the widespread groundwater populations of the D. crassicaudis species complex, which can be successfully breed in the lab, may provide a reasonable approach to assess the ecological effects of anthropogenic stressors in groundwater ecosystems.
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http://dx.doi.org/10.1016/j.chemosphere.2021.129911DOI Listing
July 2021

Measurement of the Effects of Metals on Taxis-to-Food Behavior in Caenorhabditis elegans.

Curr Protoc 2021 May;1(5):e131

Department of Biology & CESAM (Centre for Environmental and Marine Studies), University of Aveiro, Aveiro, Portugal.

Chemosensation in nematodes is linked to processes that affect their ability to survive, such as the search for food and the avoidance of toxic substances. Since the 1970s, numerous studies have assessed chemotaxis in the nematode species Caenorhabditis elegans, focusing on a multitude of agents, including bacteria (food), ions, salts, hormones, volatile organic compounds, and, to a lesser extent, metal-contaminated medium/food. The few studies evaluating metal exposure have reported a variety of responses (neutral, attraction, avoidance), which generally appear to be contaminant and/or concentration specific. Differences in experimental designs, however, hinder appropriate comparison of the findings and attainment of firm conclusions. Therefore, we herein propose and describe a detailed protocol for the assessment of the effects of metals on taxis-to-food behavior in C. elegans. Distinct approaches are proposed in two innovative stages of testing to (1) screen metals' effects on taxis-to-food behavior and (2) classify the behavioral response as attraction/avoidance/indifference or preference. Use of such a standard protocol will allow for easy comparison across studies and direct interpretation of results. Findings using this model system can contribute to a deeper understanding of the real risks of metal contamination to nematodes and how such contaminants could impact ecosystems in general, given the key environmental roles that these organisms play. © 2021 Wiley Periodicals LLC. Basic Protocol: Assessing the effects of metal contamination on taxis-to-food behavior in Caenorhabditis elegans Support Protocol 1: Synchronization of C. elegans by hand-picking gravid worms Support Protocol 2: Synchronization of C. elegans by using a bleaching solution.
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http://dx.doi.org/10.1002/cpz1.131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243080PMC
May 2021

Overview of Chemotaxis Behavior Assays in Caenorhabditis elegans.

Curr Protoc 2021 May;1(5):e120

Department of Biology & Centre for Environmental and Marine Studies (CESAM), University of Aveiro, Aveiro, Portugal.

Environmental pollution related to anthropogenic pressures, and the associated repercussions on public health, represent a worldwide problem. Thus, the study of the effects that environmental contaminants can pose to natural ecosystems and human health is of vital importance. Laboratory model organisms such as Caenorhabditis elegans have played a significant role in clarifying multilevel effects of those agents. Although the evaluation of contaminant effects at the behavioral level of organisms is an emerging approach in ecotoxicology, studies assessing chemotaxis behavior in C. elegans within the ecotoxicological research context are still scarce. Chemotaxis studies in C. elegans have contributed to the understanding of both the neuronal mechanisms involved in the behavioral effects triggered by environmental cues and the impact of contaminants on natural ecosystems. Its compact and well-characterized nervous system, as well as the availability of transgenic strains and molecular tools, allows a detailed examination of behavioral, molecular, and genetic chemosensation mechanisms. This overview provides a summary and general comparison of methods used to measure chemotaxis behavior in C. elegans, with the aim of helping researchers select the most suitable approach in their chemotaxis studies. We compare methods based on the type of chemical tested, advantages and drawbacks of the different approaches, and specific experimental goals. Lastly, we hope to encourage the evaluation of C. elegans chemotaxis behavior in ecotoxicology studies, as well as its potential integration in standardized protocols assessing environmental quality. © 2021 Wiley Periodicals LLC.
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http://dx.doi.org/10.1002/cpz1.120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162703PMC
May 2021

Cytotoxic effects of wildfire ashes: In-vitro responses of skin cells.

Environ Pollut 2021 Apr 30;285:117279. Epub 2021 Apr 30.

CESAM (Centre for Environmental and Marine Studies), University of Aveiro, Aveiro, Portugal; Department of Environment and Planning, University of Aveiro, Aveiro, Portugal.

Wildfires are a complex environmental problem worldwide. The ashes produced during the fire bear metals and PAHs with high toxicity and environmental persistence. These are mobilized into downhill waterbodies, where they can impair water quality and human health. In this context, the present study aimed at assessing the toxicity of mimicked wildfire runoff to human skin cells, providing a first view on the human health hazardous potential of such matrices. Human keratinocytes (HaCaT) were exposed to aqueous extracts of ashes (AEA) prepared from ash deposited in the soil after wildfires burned a pine or a eucalypt forest stand. Cytotoxicity (MTT assay) and changes in cell cycle dynamics (flow cytometry) were assessed. Cell viability decreased with increasing concentrations of AEA, regardless of the ash source, the extracts preparation method (filtered or unfiltered to address the dissolved or the total fractions of contaminants, respectively) or the exposure period (24 and 48 h). The cells growth was also negatively affected by the tested AEA matrices, as evidenced by a deceleration of the progress through the cell cycle, namely from phase G0/G1 to G2. The cytotoxicity of AEA could be related to particulate and dissolved metal content, but the particles themselves may directly affect the cell membrane. Eucalypt ash was apparently more cytotoxic than pine ash due to differential ash metal burden and mobility to the water phase. The deceleration of the cell cycle can be explained by the attempt of cells to repair metal-induced DNA damage, while if this checkpoint and repair pathways are not well coordinated by metal interference, genomic instability may occur. Globally, our results trigger public health concerns since the burnt areas frequently stand in slopes of watershed that serve as recreation sites and sources of drinking water, thus promoting human exposure to wildfire-driven contamination.
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http://dx.doi.org/10.1016/j.envpol.2021.117279DOI Listing
April 2021

Cortical Networks Underpinning Compensation of Verbal Fluency in Normal Aging.

Cereb Cortex 2021 Jul;31(8):3832-3845

Department of Clinical Psychology, Psychobiology and Methodology, Faculty of Health Science, Section of Psychology and Speech Therapy, University of La Laguna, La Laguna, Tenerife 38 200, Spain.

Elucidating compensatory mechanisms underpinning phonemic fluency (PF) may help to minimize its decline due to normal aging or neurodegenerative diseases. We investigated cortical brain networks potentially underpinning compensation of age-related differences in PF. Using graph theory, we constructed networks from measures of thickness for PF, semantic, and executive-visuospatial cortical networks. A total of 267 cognitively healthy individuals were divided into younger age (YA, 38-58 years) and older age (OA, 59-79 years) groups with low performance (LP) and high performance (HP) in PF: YA-LP, YA-HP, OA-LP, OA-HP. We found that the same pattern of reduced efficiency and increased transitivity was associated with both HP (compensation) and OA (aberrant network organization) in the PF and semantic cortical networks. When compared with the OA-LP group, the higher PF performance in the OA-HP group was associated with more segregated PF and semantic cortical networks, greater participation of frontal nodes, and stronger correlations within the PF cortical network. We conclude that more segregated cortical networks with strong involvement of frontal nodes seemed to allow older adults to maintain their high PF performance. Nodal analyses and measures of strength were helpful to disentangle compensation from the aberrant network organization associated with OA.
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http://dx.doi.org/10.1093/cercor/bhab052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258442PMC
July 2021

Sex differences in CSF biomarkers for neurodegeneration and blood-brain barrier integrity.

Alzheimers Dement (Amst) 2021 17;13(1):e12141. Epub 2021 Mar 17.

Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology the Sahlgrenska Academy at the University of Gothenburg Mölndal Sweden.

Introduction: As cerebrospinal fluid (CSF) neurofilament light protein (NfL) and the CSF/serum albumin ratio (Q) are used in the clinical routine, the impact of demographic factors on these biomarkers is important to understand.

Methods: Participants were derived from two Swedish samples: the population-based H70 Study (n = 308, age 70) and a clinical routine cohort (CSF NfL, n = 8995, Q, n = 39252, age 0 to 95). In the population-based study, Q and NfL were examined in relation to sex, cardiovascular risk factors, and cerebral white matter lesions (WMLs). In the clinical cohort, Q and NfL sex differences were tested in relation to age.

Results: Men had higher Q and NfL concentrations and had higher Q and NfL concentrations from adolescence throughout life. NfL was not related to WML, but Q correlated positively with WMLs.

Discussion: The CSF NfL sex difference could not be explained by vascular pathology. Future studies should consider using different reference limits for men and women.
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http://dx.doi.org/10.1002/dad2.12141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968119PMC
March 2021

GCsnap: Interactive Snapshots for the Comparison of Protein-Coding Genomic Contexts.

Authors:
Joana Pereira

J Mol Biol 2021 May 15;433(11):166943. Epub 2021 Mar 15.

Department of Protein Evolution, Max Planck Institute for Developmental Biology, Tübingen, Germany.

The biological function and evolutionary history of protein-coding genes are not only written in their nucleotide sequences. The comparison of genomic contexts throughout different lineages may highlight genomic mechanisms in the generation of new protein families, while the conservation of gene clusters may unravel, for instance, metabolic pathways. Various tools and databases exist that allow for the analysis and comparison of genomic contexts, but each has its own limitations. Online databases allow for quick comparisons, but only for those genomes for which data were pre-calculated. More advanced tools may allow for the comparison of any genome, but are often limited to a given phylogenetic kingdom or provide only a snapshot of the genomic contexts without further information about the genes involved. Here, we introduce GCsnap, a flexible Python-based tool that allows for the interactive comparison of the genomic contexts of protein-coding genes from any genome at any taxonomic level, integrating them with functional and structural information. By connecting the output to different protein databases, users can navigate through the different genomic contexts from a simple interactive platform, facilitating the further analysis of the contexts found. GCsnap is not limited to a single input format, can perform batch jobs and accepts protein classification maps. Results are stored in detailed, human and machine-readable files, and customizable, publication-ready figures. GCsnap is freely available from https://github.com/JoanaMPereira/GCsnap and can be set up easily on any computer.
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http://dx.doi.org/10.1016/j.jmb.2021.166943DOI Listing
May 2021

Effects of post-fire contamination in sediment-dwelling species of riverine systems.

Sci Total Environ 2021 Jun 27;771:144813. Epub 2021 Jan 27.

Department of Environment and Planning and Centre for Environmental and Marine Studies (CESAM), University of Aveiro, Aveiro, Portugal. Electronic address:

Wildfires are an important environmental problem in forested watersheds and can significantly alter water quality. Besides the reported ecotoxicological effects on pelagic species, the accumulation of post-fire contaminants in river sediments can also impair the benthic species. In this study, three sediment-dwelling species, Chironomus riparius, Atyaephyra desmarestii and Echinogammarus meridionalis, with different sensitivities, habitats, behaviours and/or feeding strategies, were exposed to water and sediments, in in-situ and in laboratory. Four sites were selected in a partially burnt basin (Alfusqueiro river basin), within and upstream the burnt area. The sites within the burnt area showed higher metal burden in both water and sediment, as well as changes in water physico-chemistry, consistently with the typical effects of incoming post-fire runoff. Both in-situ and laboratory exposures to water and sediments affected by the wildfire induced post-exposure feeding inhibition in the three tested macroinvertebrates. In fact, laboratory and field bioassays have produced generally consistent post-exposure feeding inhibition responses, but the most impactful response could be recognised after in-situ bioassays at the river site within the burnt area, where the species respond to the physico-chemical fluctuations during the exposure period. This comparative perspective supports the importance of using in-situ bioassays as a more realistic approach when dealing with complex and intermittent natural samples such as those affected by post-fire runoff. Overall, our results reinforce the awareness about the negative effects of wildfires on benthic biota, with significant feeding depression and consequent reduction in the available energy budget to ensure successful detoxification, growth and reproduction signalling potential trophic and functional disruption at the ecosystem level. In addition, the duality conditions of sediments as a sink and source of contaminants reinforce concerns, as the exposure of benthic organisms may persist in the long term, even after runoff income ceases due to the resuspension of contaminated sediments.
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http://dx.doi.org/10.1016/j.scitotenv.2020.144813DOI Listing
June 2021

Early stages of tau pathology and its associations with functional connectivity, atrophy and memory.

Brain 2021 Mar 16. Epub 2021 Mar 16.

Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, 223 62 Lund, Sweden.

In Alzheimer's disease, postmortem studies have shown that the first cortical site where neurofibrillary tangles appear is the transentorhinal region, a subregion within the medial temporal lobe that largely overlaps with area 35, and the entorhinal cortex. Here we used tau-PET imaging to investigate the sequence of tau pathology progression within the human medial temporal lobe and across regions in the posterior-medial system. Our objective was to study how medial temporal tau is related to functional connectivity, regional atrophy, and memory performance. We included 215 β-amyloid negative cognitively unimpaired, 81 β-amyloid positive cognitively unimpaired and 87 β-amyloid positive individuals with mild cognitive impairment, who each underwent [18]F-RO948 tau and [18]F-flutemetamol amyloid PET imaging, structural T1-MRI and memory assessments as part of the Swedish BioFINDER-2 study. First, event-based modelling revealed that the entorhinal cortex and area 35 show the earliest signs of tau accumulation followed by the anterior and posterior hippocampus, area 36 and the parahippocampal cortex. In later stages, tau accumulation became abnormal in neocortical temporal and finally parietal brain regions. Second, in cognitively unimpaired individuals, increased tau load was related to local atrophy in the entorhinal cortex, area 35 and the anterior hippocampus and tau load in several anterior medial temporal lobe subregions was associated with distant atrophy of the posterior hippocampus. Tau load, but not atrophy, in these regions was associated with lower memory performance. Further, tau-related reductions in functional connectivity in critical networks between the medial temporal lobe and regions in the posterior-medial system were associated with this early memory impairment. Finally, in patients with mild cognitive impairment, the association of tau load in the hippocampus with memory performance was partially mediated by posterior hippocampal atrophy. In summary, our findings highlight the progression of tau pathology across medial temporal lobe subregions and its disease-stage specific association with memory performance. While tau pathology might affect memory performance in cognitively unimpaired individuals via reduced functional connectivity in critical medial temporal lobe-cortical networks, memory impairment in mild cognitively impaired patients is associated with posterior hippocampal atrophy.
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http://dx.doi.org/10.1093/brain/awab114DOI Listing
March 2021

FISH in Suspension or in Adherent Cells.

Methods Mol Biol 2021 ;2246:51-67

Water Research Institute C.N.R., Monterotondo, Italy.

Fluorescence in situ hybridization (FISH) enables the detection and enumeration of microorganisms in a diversity of samples. Short-length oligonucleotide DNA probes complementary to 16S or 23S rRNA sequences are generally used to target different phylogenetic levels. The protocol for the application of FISH to aggregated or suspended cells in mixed microbial communities is described in this chapter, with a special emphasis on environmental samples.
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http://dx.doi.org/10.1007/978-1-0716-1115-9_4DOI Listing
March 2021

Effects of amyloid pathology and the APOE ε4 allele on the association between cerebrospinal fluid Aβ38 and Aβ40 and brain morphology in cognitively normal 70-years-olds.

Neurobiol Aging 2021 05 12;101:1-12. Epub 2021 Jan 12.

Region Västra Götaland, Sahlgrenska University Hospital, Psychiatry Cognition and Old Age Psychiatry Clinic, Mölndal, Sweden; Neuropsychiatric Epidemiology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, Centre for Ageing and Health (AGECAP) at the University of Gothenburg, Mölndal, Sweden.

The association between cerebrospinal fluid (CSF) amyloid beta (Aβ) Aβ38 or Aβ40 and brain grey- and white matter integrity is poorly understood. We studied this in 213 cognitively normal 70-year-olds, and in subgroups defined by presence/absence of the APOE ε4 allele and Aβ pathology: Aβ-/APOE-, Aβ+/APOE-, Aβ-/APOE+ and Aβ+/APOE+. CSF Aβ was quantified using ELISA and genotyping for APOE was performed. Low CSF Aβ42 defined Aβ plaque pathology. Brain volumes were assessed using Freesurfer-5.3, and white matter integrity using tract-based statistics in FSL. Aβ38 and Aβ40 were positively correlated with cortical thickness, some subcortical volumes and white matter integrity in the total sample, and in 3 of the subgroups: Aβ-/APOE-, Aβ+/APOE- and Aβ-/APOE+. In Aβ+/APOE+ subjects, higher Aβ38 and Aβ40 were linked to reduced cortical thickness and subcortical volumes. We hypothesize that production of all Aβ species decrease in brain regions with atrophy. In Aβ+/APOE+, Aβ-dysregulation may be linked to cortical atrophy in which high Aβ levels is causing pathological changes in the gray matter of the brain.
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http://dx.doi.org/10.1016/j.neurobiolaging.2020.10.033DOI Listing
May 2021

Lenstar LS 900 versus Pentacam-AXL: analysis of refractive outcomes and predicted refraction.

Sci Rep 2021 Jan 14;11(1):1449. Epub 2021 Jan 14.

Ophthalmology Department, Centro Hospitalar Leiria, Rua das Olhalvas, 2410-197, Leiria, Portugal.

Analysis of refractive outcomes, using biometry data collected with a new biometer (Pentacam-AXL, OCULUS, Germany) and a reference biometer (Lenstar LS 900, HAAG-STREIT AG, Switzerland), in order to assess differences in the predicted and actual refraction using different formulas. Prospective, institutional study, in which intraocular lens (IOL) calculation was performed using the Haigis, SRK/T and Hoffer Q formulas with the two systems in patients undergoing cataract surgery between November 2016 and August 2017. Four to 6 weeks after surgery, the spherical equivalent (SE) was derived from objective refraction. Mean prediction error (PE), mean absolute error (MAE) and the median absolute error (MedAE) were calculated. The percentage of eyes within ± 0.25, ± 0.50, ± 1.00, and ± 2.00 D of MAE was determined. 104 eyes from 76 patients, 35 males (46.1%), underwent uneventful phacoemulsification with IOL implantation. Mean SE after surgery was - 0.29 ± 0.46 D. Mean prediction error (PE) using the SRK/T, Haigis and Hoffer Q formulas with the Lenstar was significantly different (p > 0.0001) from PE calculated with the Pentacam in all three formulas. Percentage of eyes within ± 0.25 D MAE were larger with the Lenstar device, using all three formulas. The difference between the actual refractive error and the predicted refractive error is consistently lower when using Lenstar. The Pentacam-AXL user should be alert to the critical necessity of constant optimization in order to obtain optimal refractive results.
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http://dx.doi.org/10.1038/s41598-021-81146-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809453PMC
January 2021

The VCBS superfamily forms a third supercluster of β-propellers that includes tachylectin and integrins.

Bioinformatics 2021 Jan 8. Epub 2021 Jan 8.

Department of Protein Evolution, Max-Planck-Institute for Developmental Biology, Tübingen, 72076, Germany.

Motivation: β-Propellers are found in great variety across all kingdoms of life. They assume many cellular roles, primarily as scaffolds for macromolecular interactions and catalysis. Despite their diversity, most β-propeller families clearly originated by amplification from the same ancient peptide-the "blade". In cluster analyses, β-propellers of the WD40 superfamily always formed the largest group, to which some important families, such as the α-integrin, Asp-box, and glycoside hydrolase β-propellers connected weakly. Motivated by the dramatic growth of sequence databases we revisited these connections, with a special focus on VCBS-like β-propellers, which have not been analysed for their evolutionary relationships so far.

Results: We found that VCBS-like form a supercluster with integrin-like β-propellers and tachylectins, clearly delimited from the superclusters formed by WD40 and Asp-Box β-propellers. Connections between the three superclusters are made mainly through PQQ-like β-propeller. Our results present a new, greatly expanded view of the β-propeller classification landscape.

Supplementary Information: Supplementary data are available at Bioinformatics online.
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http://dx.doi.org/10.1093/bioinformatics/btaa1085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8023676PMC
January 2021

Subcutaneous Implantation Assessment of New Calcium-Silicate Based Sealer for Warm Obturation.

Biomedicines 2021 Jan 1;9(1). Epub 2021 Jan 1.

Coimbra Institute for Clinical and Biomedical Research (iCBR) and Institute of Biophysics, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal.

Calcium silicate-based sealers were recently introduced as a new class of endodontic sealers, with potential further benefits due to their bioactivity. The aim of this study was to evaluate the biocompatibility of two new hydraulic calcium silicate-based sealers, TotalFill BC Sealer (FKG, La Chaux-des-Fonds, Switzerland) and TotalFill BC Sealer HiFlow (FKG, La Chaux-des-Fonds, Switzerland) through subcutaneous implantation in connective tissue of rats. Subcutaneous implantation was performed in 16 young Wistar rats. Four polyethylene tubes were implanted in each animal, one empty to serve as a control, and three filled with tested sealers: AH Plus as reference (Dentsply DeTrey, Konstanz, Germany), TotalFill BC Sealer (BC) and TotalFill BC Sealer HiFlow (HiFlow). Eight rats were euthanized at 8 days and the remaining eight at 30 days. Hematoxylin-eosin staining was used to score the inflammatory reaction, macrophage infiltrate and to measure the thickness of the fibrous capsule. von Kossa staining was performed to evaluate the mineralization level. Kruskal-Wallis test followed by Dunn's test was used to analyze non-parametric data. To analyze the influence of the implantation time within each material, a Mann-Whitney U test was performed. At eight days post-implantation, AH Plus induced a more intense inflammatory reaction when compared both with the control ( ≤ 0.001) and BC ( ≤ 0.01). HiFlow presented a higher score of macrophage infiltrate than control ( ≤ 0.01) and BC ( ≤ 0.05). The fibrous capsule thickness in this period was significantly higher for the BC group when compared to control ( ≤ 0.01) and AH Plus ( ≤ 0.05). The mineralization potential was higher for the HiFlow group when compared with the control ( ≤ 0.001) and AH Plus ( ≤ 0.001). At 30 days post-implantation, the score for the inflammatory reaction remained higher for the AH Plus group when compared both to control ( ≤ 0.01) and BC ( ≤ 0.001). The macrophage infiltrate of the HiFlow was significantly higher than control ( ≤ 0.001) and AH Plus groups ( ≤ 0.01), additionally, the fibrous capsule of the BC ( ≤ 0.001) and HiFlow ( ≤ 0.01) groups were both thicker than control. Mineralization potential was observed only on BC ( ≤ 0.05) and HiFlow groups ( ≤ 0.001), when compared to control). BC exhibited the best biocompatibility performance of all tested sealers and HiFlow provided the greatest induction of mineralized tissues. Both TotalFill BC Sealer and TotalFill BC Sealer HiFlow are biocompatible and show potential bioactivity when implanted in the subcutaneous tissue. Bioactivity was not found in AH Plus.
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http://dx.doi.org/10.3390/biomedicines9010024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824331PMC
January 2021

Evaluation of Saliva Stability for NMR Metabolomics: Collection and Handling Protocols.

Metabolites 2020 Dec 19;10(12). Epub 2020 Dec 19.

CICECO-Department of Chemistry, Aveiro Institute of Materials, Campus Universitário de Santiago, University of Aveiro, 3810-193 Aveiro, Portugal.

Maintaining a salivary metabolic profile upon sample collection and preparation is determinant in metabolomics. Nuclear magnetic resonance (NMR) spectroscopy was used to identify metabolite changes during short-term storage, at room temperature (RT)/4 °C/-20 °C, and after sample preparation, at RT/4 °C (mimicking typical clinical/laboratory settings). Interestingly, significant metabolic inter-individual and inter-day variability were noted, probably determining sample stability to some extent. After collection, no changes were noted at -20 °C (at least for 4 weeks). RT storage induced decreases in methylated macromolecules (6 h); lactate (8 h); alanine (12 h); galactose, hypoxanthine, pyruvate (24 h); sarcosine, betaine, choline, -acetyl-glycoproteins (48 h), while acetate increased (48 h). Less, but different, changes were observed at 4 °C, suggesting different oral and microbial status at different temperatures (with a possible contribution from inter-individual and inter-day variability), and identifying galactose, hypoxanthine, and possibly, choline esters, as potential general stability indicators. After preparation, addition of NaN did not impact significantly on saliva stabilization, neither at RT nor at 4 °C, although its absence was accompanied by slight increases in fucose (6.5 h) and proline (8 h) at RT, and in xylose (24 h) at 4 °C. The putative metabolic origins of the above variations are discussed, with basis on the salivary microbiome. In summary, after collection, saliva can be stored at RT/4 °C for up to 6 h and at -20 °C for at least 4 weeks. Upon preparation for NMR analysis, samples are highly stable at 25 °C up to 8 h and at 4 °C up to 48 h, with NaN addition preventing possible early changes in fucose, proline (6-8 h), and xylose (24 h) levels.
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http://dx.doi.org/10.3390/metabo10120515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7766053PMC
December 2020

The Upper Digestive Tract Microbiome and Oesophageal Squamous Cell Carcinoma: Epidemiology, Pathogenesis, and Clinical Implications in Africa.

Pathobiology 2021 8;88(2):141-155. Epub 2020 Dec 8.

Grupo de Patologia e Terapêutica Experimental e Departamento de Oncologia do Instituto Português de Oncologia do Porto, Porto, Portugal,

The study of the microbiome has significantly contributed to our understanding of complex diseases including cancer, with a profound influence of the microbiota on clinical prognosis and the efficacy of cancer treatments. Oesophageal cancer is positioned amongst the most aggressive malignant diseases, resulting from a complex interaction between anthropometric, genetic, immune response, and environmental factors. Oesophageal squamous cell carcinoma (OSCC) is the most common type of oesophageal cancer and is a serious burden in Eastern Africa, in the area known as the African oesophageal cancer corridor (AOCC). OSCC is often diagnosed at a late stage, with patients already suffering from severe malnutrition and dehydration due to swallowing difficulties, leading to high mortality rates. So far, aetiological factors have been individually analysed with an inappropriate contextualisation. The upper digestive tract microbiome has been proposed to contribute to the onset and progression of OSCC but with limited understanding of the mechanisms behind this interaction. Data on African populations are limited, and the aetiology of AOCC is still poorly understood. This review discusses the current knowledge of the aetiology of OSCC in Africa, with special focus on the probable influence of the upper digestive tract microbiota.
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http://dx.doi.org/10.1159/000511422DOI Listing
December 2020

Untangling the association of amyloid-β and tau with synaptic and axonal loss in Alzheimer's disease.

Brain 2021 02;144(1):310-324

Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Malmö, Sweden.

It is currently unclear how amyloid-β and tau deposition are linked to changes in synaptic function and axonal structure over the course of Alzheimer's disease. Here, we assessed these relationships by measuring presynaptic (synaptosomal-associated protein 25, SNAP25; growth-associated protein 43, GAP43), postsynaptic (neurogranin, NRGN) and axonal (neurofilament light chain) markers in the CSF of individuals with varying levels of amyloid-β and tau pathology based on 18F-flutemetamol PET and 18F-flortaucipir PET. In addition, we explored the relationships between synaptic and axonal markers with cognition as well as functional and anatomical brain connectivity markers derived from resting-state functional MRI and diffusion tensor imaging. We found that the presynaptic and postsynaptic markers SNAP25, GAP43 and NRGN are elevated in early Alzheimer's disease i.e. in amyloid-β-positive individuals without evidence of tau pathology. These markers were associated with greater amyloid-β pathology, worse memory and functional changes in the default mode network. In contrast, neurofilament light chain was abnormal in later disease stages, i.e. in individuals with both amyloid-β and tau pathology, and correlated with more tau and worse global cognition. Altogether, these findings support the hypothesis that amyloid-β and tau might have differential downstream effects on synaptic and axonal function in a stage-dependent manner, with amyloid-related synaptic changes occurring first, followed by tau-related axonal degeneration.
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http://dx.doi.org/10.1093/brain/awaa395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8210638PMC
February 2021

Metabolic and appetite effects of fructose and glucose in subjects with type 1 diabetes: a randomized crossover clinical trial.

Curr Diabetes Rev 2020 11 30. Epub 2020 Nov 30.

Federal University of Rio de Janeiro, Nutrition Institute Josué de Castro, Rio de Janeiro, RJ. Brazil.

Background: Fructose has been widely used for producing lower post-infusion glucose increase than other carbohydrates, but seems that it promotes an increase in post-infusion triglycerides.

Objective: The present study investigated the effects of fructose and glucose in metabolic variables and appetite sensations in patients with type 1 diabetes mellitus (T1DM).

Methods: This is a single-blind, randomized and crossover study (washout of 1-5 weeks), which has evaluated 16 adult T1DM patients, accompanied at University Hospital. After eight hours overnight fasting, were assessment of capillary blood glucose, anthropometric variables, appetite sensations and laboratory tests (glycemia, lipemia, leptin and glucagon). Subsequently, they received 200mL of solutions with water and 75g of crystal fructose or glucose. Appetite sensations and capillary blood glucose were evaluated in different post-infusion times. Blood was drawn after 180 minutes for the laboratory tests.

Results: Blood glucose increased after the intake of both solutions, but the glucose induced a higher elevation. None of them increased triglycerides or glucagon. Glucagon maintenance was similar among the solutions. Furthermore, both solutions reduced leptin and increased fullness, but only fructose increased lack of interest in eating sweets.

Conclusions: Fructose induced smaller increase in postprandial blood glucose than glucose, without changes in triglycerides and glucagon. In addition, leptin levels and appetite sensations were similar to glucose. Other studies are needed in order to confirm these findings, especially in the long term, so that their use becomes really reliable.
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http://dx.doi.org/10.2174/1573399816666201201092334DOI Listing
November 2020