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1.
iScience ; 27(1): 108671, 2024 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-38292167

RESUMEN

Alzheimer's disease (AD) is a multifactorial pathology, with most cases having a sporadic origin. Recently, knock-in (KI) mouse models, such as the novel humanized amyloid-ß (hAß)-KI, have been developed to better resemble sporadic human AD. METHODS: Here, we compared hippocampal publicly available transcriptomic profiles of transgenic (5xFAD and APP/PS1) and KI (hAß-KI) mouse models with early- (EOAD) and late- (LOAD) onset AD patients. RESULTS: The three mouse models presented more Gene Ontology biological processes terms and enriched signaling pathways in common with LOAD than with EOAD individuals. Experimental validation of consistently dysregulated genes revealed five altered in mice (SLC11A1, S100A6, CD14, CD33, and C1QB) and three in humans (S100A6, SLC11A1, and KCNK). Finally, we identified 17 transcription factors potentially acting as master regulators of AD. CONCLUSION: Our cross-species analyses revealed that the three mouse models presented a remarkable similarity to LOAD, with the hAß-KI being the more specific one.

2.
Rev. ADM ; 80(5): 247-254, sept.-oct. 2023. ilus, tab, graf
Artículo en Español | LILACS | ID: biblio-1530692

RESUMEN

Introducción: la periodontitis es una enfermedad infecciosa multifactorial asociada a un biofilm de microorganismos patógenos. Objetivo: el objetivo del trabajo fue establecer la prevalencia de Porphyromonas gingivalis en pacientes con periodontitis y relacionarla con la severidad de la enfermedad. Material y métodos: participaron 45 pacientes, sistémicamente saludables, con edades entre 35 y 65 años. El grado de periodontitis se definió según los criterios de Papapanou y colaboradores. Como grupo control, se incluyeron 20 sujetos de ambos sexos sin periodontitis y sin enfermedades sistémicas. Se tomaron muestras de fluido gingival en dos sitios más profundos. Porphyromonas gingivalis se detectó por PCR (reacción en cadena de la polimerasa). Resultados: la frecuencia relativa de periodontitis fue de 13.3% grado I, 46.7% grado II y 40% grado III. El sexo masculino presentó periodontitis grado III 72.2% y grado II 52.3%. El grado I se registró con mayor frecuencia en el sexo femenino, 66.7%. La prevalencia de Porphyromonas gingivalis en la población con periodontitis fue de 44.4%. Se obtuvieron diferencias estadísticamente significativas entre los grados de severidad de periodontitis y la presencia de Porphyromonas gingivalis (p = 0.0002, α = 5%). Conclusión: la periodontitis predominó en el sexo masculino. La prevalencia de Porphyromonas gingivalis en la población con periodontitis crónica fue de 44.4% y su presencia está relacionada con la severidad (AU)


Introduction: periodontitis is a multifactorial infectious disease associated with a biofilm of pathogenic microorganisms. Objective: the objective of the work was to establish the prevalence of Porphyromonas gingivalis in patients with periodontitis and relate it to the severity of the disease. Material and methods: 45 systemically healthy patients, aged between 35 and 65 years old, participated. The degree of periodontitis was defined according to the criteria of Papapanou et al. As a control group, 20 patients of both sexes without periodontitis and without systemic diseases were included. Gingival fluid samples were taken from two deeper sites. Porphyromonas gingivalis was detected by PCR (polymerase chain reaction). Results: the relative frequency of periodontitis was 13.3% grade I, 46.7% grade II and 40% grade III. The male sex presented periodontitis grade III 72.2% and grade II 52.3%. Grade I was recorded more frequently in the female sex, 66.7%. The prevalence of Porphyromonas gingivalis in the population with periodontitis was 44.4%. Statistically significant differences were obtained between the degrees of severity of periodontitis and the presence of Porphyromonas gingivalis (p = 0.0002, α = 5%). Conclusion: periodontitis predominated in males. The prevalence of Porphyromonas gingivalis in the population with chronic periodontitis was 44.4% and its presence is related to severity (AU)


Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Porphyromonas gingivalis/aislamiento & purificación , Periodontitis Crónica/epidemiología , Argentina/epidemiología , Facultades de Odontología , Epidemiología Descriptiva , Estudios Transversales , Distribución por Edad y Sexo , Cetrimonio
3.
Viruses ; 15(2)2023 01 22.
Artículo en Inglés | MEDLINE | ID: mdl-36851525

RESUMEN

The COVID-19 pandemic has lately been driven by Omicron. This work aimed to study the dynamics of SARS-CoV-2 Omicron lineages during the third and fourth waves of COVID-19 in Argentina. Molecular surveillance was performed on 3431 samples from Argentina, between EW44/2021 and EW31/2022. Sequencing, phylogenetic and phylodynamic analyses were performed. A differential dynamic between the Omicron waves was found. The third wave was associated with lineage BA.1, characterized by a high number of cases, very fast displacement of Delta, doubling times of 3.3 days and a low level of lineage diversity and clustering. In contrast, the fourth wave was longer but associated with a lower number of cases, initially caused by BA.2, and later by BA.4/BA.5, with doubling times of about 10 days. Several BA.2 and BA.4/BA.5 sublineages and introductions were detected, although very few clusters with a constrained geographical distribution were observed, suggesting limited transmission chains. The differential dynamic could be due to waning immunity and an increase in population gatherings in the BA.1 wave, and a boosted population (for vaccination or recent prior immunity for BA.1 infection) in the wave caused by BA2/BA.4/BA.5, which may have limited the establishment of the new lineages.


Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/epidemiología , Argentina/epidemiología , Pandemias , Filogenia
4.
Front Psychol ; 13: 1036669, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36337485

RESUMEN

Training can influence behavioral performance and lead to brain reorganization. In particular, training in one modality, for example, auditory, can improve performance in another modality, for example, visual. Previous research suggests that one of the mechanisms behind this phenomenon could be the cross-modal recruitment of the sensory areas, for example, the auditory cortex. Studying expert musicians offers a chance to explore this process. Rhythm is an aspect of music that can be presented in various modalities. We designed an fMRI experiment in which professional pianists and non-musicians discriminated between two sequences of rhythms presented auditorily (series of sounds) or visually (series of flashes). Behavioral results showed that musicians performed in both visual and auditory rhythmic tasks better than non-musicians. We found no significant between-group differences in fMRI activations within the auditory cortex. However, we observed that musicians had increased activation in the right Inferior Parietal Lobe when compared to non-musicians. We conclude that the musicians' superior visual rhythm discrimination is not related to cross-modal recruitment of the auditory cortex; instead, it could be related to activation in higher-level, multimodal areas in the cortex.

5.
Neurology ; 99(22): e2428-e2436, 2022 11 29.
Artículo en Inglés | MEDLINE | ID: mdl-36266044

RESUMEN

BACKGROUND AND OBJECTIVES: To assess the concordance and discordance between the core Alzheimer disease (AD) CSF biomarkers and [18F]fluorodeoxyglucose (FDG)-PET patterns evaluated clinically in memory clinic patients who meet appropriate use criteria for AD biomarker investigations. METHODS: We retrospectively assessed participants with atypical and/or early-onset dementia evaluated at a tertiary care memory clinic. All individuals underwent CSF evaluations for Aß42, phosphorylated tau (P-tau181) and total tau, and brain [18F]FDG-PET. [18F]FDG-PET data were visually interpreted by 2 nuclear medicine experts as being consistent with AD or non-AD. CSF biomarker results were similarly grouped into AD biomarker positive/negative. Contingency tables and Kappa coefficients were used to establish the level of agreement and disagreement between CSF and [18F]FDG-PET results in all individuals. RESULTS: One hundred thirty-six individuals had both [18F]FDG-PET and lumbar puncture performed as part of the early-onset and/or atypical dementia assessments. [18F]FDG-PET showed a pattern suggestive of AD in 43% of patients, while CSF biomarkers showed results consistent with AD in 57% of participants. In patients who met criteria for AD biomarker investigations, we found that [18F]FDG-PET was discordant with CSF AD biomarkers in nearly 20% of cases; 12% of individuals with [18F]FDG-PET scans consistent with AD had AD-negative CSF results; and 7% of individuals with [18F]FDG-PET scans not consistent with AD had AD-positive CSF results, potentially suggesting atypical AD variants or less advanced neurodegeneration. [18F]FDG-PET discriminated patients with an AD-positive CSF profile from patients with an AD-negative profile with a sensitivity and specificity higher than 80% (sensitivity: 81%, 95% CI = 71-88%, SP: 81%, 95% CI = 68-89%). Furthermore, [18F]FDG-PET had a positive predictive value of 87% (95% CI = 78-93%) and a negative predictive value of 72% (95% CI = 60-82%). DISCUSSION: CSF and [18F]FDG-PET disagreed in nearly 20% of the cases studied in this clinical series. While CSF Aß42 and P-tau181 biomarkers are specific for AD, the topographical information from [18F]FDG-PET may provide complementary information.


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Humanos , Enfermedad de Alzheimer/diagnóstico por imagen , Fluorodesoxiglucosa F18 , Proteínas tau , Péptidos beta-Amiloides , Estudios Retrospectivos , Tomografía de Emisión de Positrones , Biomarcadores , Fragmentos de Péptidos
6.
Front Neurol ; 13: 888479, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35937057

RESUMEN

Abnormalities in the expression of metabotropic glutamate receptor type 5 (mGluR5) have been observed in the hippocampus of patients with drug-resistant mesial Temporal Lobe Epilepsy (mTLE). Ex-vivo studies in mTLE hippocampal surgical specimens have shown increased mGluR5 immunoreactivity, while in vivo whole brain imaging using positron emission tomography (PET) demonstrated reduced hippocampal mGluR5 availability. To further understand mGluR5 abnormalities in mTLE, we performed a saturation autoradiography study with [3H]ABP688 (a negative mGluR5 allosteric modulator). We aimed to evaluate receptor density (Bmax) and dissociation constants (KD) in hippocampal mTLE surgical specimens and in non-epilepsy hippocampi from necropsy controls. mTLE specimens showed a 43.4% reduction in receptor density compared to control hippocampi, which was independent of age, sex and KD (multiple linear regression analysis). There was no significant difference in KD between the groups, which suggests that the decreased mGluR5 availability found in vivo with PET cannot be attributed to reduced affinity between ligand and binding site. The present study supports that changes within the epileptogenic tissue include mGluR5 internalization or conformational changes that reduce [3H]ABP688 binding, as previously suggested in mTLE patients studied in vivo.

7.
Front Psychol ; 12: 728408, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34675842

RESUMEN

In view of the COVID-19 pandemic, students had to cope with the challenging situation of handling a vast amount of potentially conflicting online information while staying informed. Reading conflicting scientific information has been shown to require cognitive effort for one to integrate it successfully, but reading such information during a crisis-such as the COVID-19 pandemic-may cause additional emotional stress, as students also had to cope with critical aspects of the pandemic (e.g., physical distancing and uncertainty). Different studies have indicated that in crises, stress can be relieved by seeking online social support (as a coping strategy). Similarly, working together (as collaborative learning) can also help people more critically discuss information on a cognitive level. Based on the approaches of online collaborative learning and online social support seeking, we were interested in whether an individual vs. collaborative communication setting would lead to any differences in students' cognitive as well as emotional engagement with conflicting information about COVID-19. In a 2 × 2 mixed design, N = 109 education science students were exposed to two conflicting texts regarding COVID-19 testing that contained current scientific information. The online experiment was conducted in Germany in April 2020, which was the beginning of lockdown in that country. After reading the two texts, participants were asked to reflect on their engagement with the conflicting information either individually (individual group, n = 49) or via chat collaboratively (collaboration group, n = 60 in 30 dyads). With respect to participants' written reflections (content-analyzed regarding cognitive as well as emotional engagement), participants in the collaborative group, compared to those in the individual group, more often discussed the pandemic in general and less often engaged emotionally when discussing the evidence from texts. All participants reported higher perceived information overload, lower self-efficacy in sourcing information about COVID-19, and higher active coping strategies after the reflection task compared to before reading the information, with no significant differences between the collaborative and individual groups. We discuss these findings regarding any opportunities and challenges that arise in online collaboration between students for cognitive and emotional engagement when handling conflicting information about COVID-19.

8.
Matrix Biol Plus ; 10: 100064, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34195596

RESUMEN

Two inherent challenges in the mechanistic interpretation of protease-deficient phenotypes are defining the specific substrate cleavages whose reduction generates the phenotypes and determining whether the phenotypes result from loss of substrate function, substrate accumulation, or loss of a function(s) embodied in the substrate fragments. Hence, recapitulation of a protease-deficient phenotype by a cleavage-resistant substrate would stringently validate the importance of a proteolytic event and clarify the underlying mechanisms. Versican is a large proteoglycan required for development of the circulatory system and proper limb development, and is cleaved by ADAMTS proteases at the Glu441-Ala442 peptide bond located in its alternatively spliced GAGß domain. Specific ADAMTS protease mutants have impaired interdigit web regression leading to soft tissue syndactyly that is associated with reduced versican proteolysis. Versikine, the N-terminal proteolytic fragment generated by this cleavage, restores interdigit apoptosis in ADAMTS mutant webs. Here, we report a new mouse transgene, Vcan AA, with validated mutations in the GAGß domain that specifically abolish this proteolytic event. Vcan AA/AA mice have partially penetrant hindlimb soft tissue syndactyly. However, Adamts20 inactivation in Vcan AA/AA mice leads to fully penetrant, more severe syndactyly affecting all limbs, suggesting that ADAMTS20 cleavage of versican at other sites or of other substrates is an additional requirement for web regression. Indeed, immunostaining with a neoepitope antibody against a cleavage site in the versican GAGα domain demonstrated reduced staining in the absence of ADAMTS20. Significantly, mice with deletion of Vcan exon 8, encoding the GAGß domain, consistently developed soft tissue syndactyly, whereas mice unable to include exon 7, encoding the GAGα domain in Vcan transcripts, consistently had fully separated digits. These findings suggest that versican is cleaved within each GAG-bearing domain during web regression, and affirms that proteolysis in the GAGß domain, via generation of versikine, has an essential role in interdigital web regression.

9.
Epilepsia ; 62(7): 1559-1568, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34060082

RESUMEN

OBJECTIVE: Previous positron emission tomography (PET) studies using [11 C]ABP688 show reduced metabotropic glutamate receptor type 5 (mGluR5) allosteric binding site availability in the epileptogenic hippocampus of mesial temporal lobe epilepsy (MTLE) patients. However, the link between mGluR5 abnormalities and postsurgical outcomes remains unclear. Here, we test whether reduced PET [11 C]ABP688 binding in cornu ammonis (CA) sectors more vulnerable to glutamatergic excitotoxicity relates to surgical outcomes. METHODS: We obtained magnetic resonance imaging (MRI) and [11 C]ABP688-PET from 31 unilateral MTLE patients and 30 healthy controls. MRI hippocampal subfields were segmented using FreeSurfer. To respect the lower PET special resolution, MRI-derived anatomical subfields were combined into CA1-3, CA4/dentate gyrus, and Subiculum. Partial volume corrected [11 C]ABP688 nondisplaceable binding potential (BPND ) values were averaged across each subfield, and Z-scores were calculated. Subfield [11 C]ABP688-BPND was compared between seizure-free and non-seizure-free patients. In addition, we also assessed subfield volumes and [18 F]fluorodeoxyglucose (FDG) uptake in each clinical group. RESULTS: MTLE [11 C]ABP688-BPND was reduced in ipsilateral (epileptogenic) CA1-3 and CA4/dentate-gyrus (p < .001, 95% confidence interval [CI] = .29-.51) compared to controls, with no difference in Subiculum. [11 C]ABP688-BPND and subfield volumes were compared between seizure-free (Engel IA, n = 13) and non-seizure-free patients (Engel IC-III, n = 10). In ipsilateral CA1-3 only, [11 C]ABP688-BPND was lower in seizure-free patients than in non-seizure-free patients (p = .012, 95% CI = 1.46-11.0) independently of volume. A subset analysis of 12 patients with [11 C]ABP688-PET+[18 F]FDG-PET showed no between-group significant difference in [18 F]FDG uptake, whereas CA1-3 [11 C]ABP688-BPND remained significantly lower in the seven of 12 seizure-free patients (p = .03, 95% CI = -3.13 to -.21). SIGNIFICANCE: Reduced mGluR5 allosteric site availability in hippocampal CA1-3, measured in vivo by [11 C]ABP688-PET, is associated with postsurgery seizure freedom independent of atrophy or hypometabolism. Information derived from hippocampal CA1-3 [11 C]ABP688-PET is a promising imaging biomarker potentially impactful in surgical decisions for MRI-negative/PET-negative MTLE patients.


Asunto(s)
Epilepsia del Lóbulo Temporal/genética , Epilepsia del Lóbulo Temporal/cirugía , Ácido Glutámico/genética , Hipocampo/metabolismo , Procedimientos Neuroquirúrgicos , Receptores de Ácido Kaínico/genética , Adolescente , Adulto , Anciano , Región CA1 Hipocampal/metabolismo , Región CA3 Hipocampal , Epilepsia del Lóbulo Temporal/diagnóstico por imagen , Femenino , Fluorodesoxiglucosa F18 , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Oximas , Tomografía de Emisión de Positrones , Piridinas , Radiofármacos , Receptores de Ácido Kaínico/metabolismo , Resultado del Tratamiento , Adulto Joven
10.
J Interpers Violence ; 36(3-4): NP1913-1940NP, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-29429389

RESUMEN

Numerous school-based prevention programs have been developed by scientists and practitioners to address sexual violence in adolescence. However, such programs struggle with two major challenges. First, the effectiveness of many well-established practitioner programs has not been rigorously evaluated. Second, effective scientific programs may be hard to implement into everyday school practice. Combining the knowledge of scientists and practitioners in a scientist-practitioner program could be a helpful compromise. The aim of the present study is to evaluate the effects of a scientist-practitioner program and a practitioner program using a cluster-randomized experimental design. Twenty-seven school classes were randomly assigned to either one of two programs or a control group. Outcome variables (knowledge, attitudes, behavior, and iatrogenic effects) were assessed at pretest, posttest, and a 6-month follow-up for 453 adolescents (55% female, Mage = 14.18). Short-term effects were found in both programs regarding general knowledge, knowledge of professional help, and victim-blaming attitudes. Long-term effects were found in both programs regarding general knowledge and knowledge of professional help and, in the practitioner program, in a reduction of victimization. No other effects were found on attitudes and behavior. No iatrogenic effects in the form of increased anxiety were found. Both the scientist-practitioner and the practitioner program show promise for the prevention of sexual violence in adolescence; in particular, the practitioner program may be a more cost-effective method.


Asunto(s)
Acoso Escolar , Víctimas de Crimen , Delitos Sexuales , Adolescente , Femenino , Conocimientos, Actitudes y Práctica en Salud , Humanos , Masculino , Evaluación de Programas y Proyectos de Salud , Servicios de Salud Escolar , Instituciones Académicas , Delitos Sexuales/prevención & control
11.
Educ Inf Technol (Dordr) ; 26(2): 2053-2089, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33013181

RESUMEN

In everyday life, people seek, evaluate, and use online sources to underpin opinions and make decisions. While education must promote the skills people need to critically question the sourcing of online information, it is important, more generally, to understand how to successfully promote the acquisition of any skills related to seeking online information. This review outlines technologies that aim to support users when they collaboratively seek online information. Upon integrating psychological-pedagogical approaches on trust in and the sourcing of online information, argumentation, and computer-supported collaborative learning, we reviewed the literature (N = 95 journal articles) on technologies for collaborative online information seeking. The technologies we identified either addressed collaborative online information seeking as an exclusive process for searching for online information or, alternatively, addressed online information seeking within the context of a more complex learning process. Our review was driven by three main research questions: We aimed to understand whether and how the studies considered 1) the role of trust and critical questioning in the sourcing of online information, 2) the learning processes at play when information seekers engage in collaborative argumentation, and 3) what affordances are offered by technologies that support users' collaborative seeking of online information. The reviewed articles that focused exclusively on technologies for seeking online information primarily addressed aspects of cooperation (e.g., task management), whereas articles that focused on technologies for integrating the processes of information seeking into the entire learning processes instead highlighted aspects of collaborative argumentation (e.g., exchange of multiple perspectives and critical questioning in argumentation). Seven of the articles referred to trust as an aspect of seekers' sourcing strategies. We emphasize how researchers', users', and technology developers' consideration of collaborative argumentation could expand the benefits of technological support for seeking online information.

12.
Brain Imaging Behav ; 15(3): 1469-1482, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32700256

RESUMEN

Early sensory deprivation, such as deafness, shapes brain development in multiple ways. Deprived auditory areas become engaged in the processing of stimuli from the remaining modalities and in high-level cognitive tasks. Yet, structural and functional changes were also observed in non-deprived brain areas, which may suggest the whole-brain network changes in deaf individuals. To explore this possibility, we compared the resting-state functional network organization of the brain in early deaf adults and hearing controls and examined global network segregation and integration. Relative to hearing controls, deaf adults exhibited decreased network segregation and an altered modular structure. In the deaf, regions of the salience network were coupled with the fronto-parietal network, while in the hearing controls, they were coupled with other large-scale networks. Deaf adults showed weaker connections between auditory and somatomotor regions, stronger coupling between the fronto-parietal network and several other large-scale networks (visual, memory, cingulo-opercular and somatomotor), and an enlargement of the default mode network. Our findings suggest that brain plasticity in deaf adults is not limited to changes in the auditory cortex but additionally alters the coupling between other large-scale networks and the development of functional brain modules. These widespread functional connectivity changes may provide a mechanism for the superior behavioral performance of the deaf in visual and attentional tasks.


Asunto(s)
Corteza Auditiva , Sordera , Adulto , Encéfalo/diagnóstico por imagen , Mapeo Encefálico , Humanos , Imagen por Resonancia Magnética , Plasticidad Neuronal
13.
Front Psychol ; 11: 572744, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33362638

RESUMEN

Many urgent problems that societies currently face-from climate change to a global pandemic-require citizens to engage with scientific information as members of democratic societies as well as to solve problems in their personal lives. Most often, to solve their epistemic aims (aims directed at achieving knowledge and understanding) regarding such socio-scientific issues, individuals search for information online, where there exists a multitude of possibly relevant and highly interconnected sources of different perspectives, sometimes providing conflicting information. The paper provides a review of the literature aimed at identifying (a) constraints and affordances that scientific knowledge and the online information environment entail and (b) individuals' cognitive and motivational processes that have been found to hinder, or conversely, support practices of engagement (such as critical information evaluation or two-sided dialogue). Doing this, a conceptual framework for understanding and fostering what we call online engagement with scientific information is introduced, which is conceived as consisting of individual engagement (engaging on one's own in the search, selection, evaluation, and integration of information) and dialogic engagement (engaging in discourse with others to interpret, articulate and critically examine scientific information). In turn, this paper identifies individual and contextual conditions for individuals' goal-directed and effortful online engagement with scientific information.

14.
Front Immunol ; 10: 829, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31040853

RESUMEN

Determining antigen specificity is vital for understanding B cell biology and for producing human monoclonal antibodies. We describe here a powerful method for identifying B cells that recognize membrane antigens expressed on cells. The technique depends on two characteristics of the interaction between a B cell and an antigen-expressing cell: antigen-receptor-mediated extraction of antigen from the membrane of the target cell, and B cell activation. We developed the method using influenza hemagglutinin as a model viral membrane antigen, and tested it using acetylcholine receptor (AChR) as a model membrane autoantigen. The technique involves co-culturing B cells with adherent, bioorthogonally labeled cells expressing GFP-tagged antigen, and sorting GFP-capturing, newly activated B cells. Hemagglutinin-specific B cells isolated this way from vaccinated human donors expressed elevated CD20, CD27, CD71, and CD11c, and reduced CD21, and their secreted antibodies blocked hemagglutination and neutralized viral infection. Antibodies cloned from AChR-capturing B cells derived from patients with myasthenia gravis bound specifically to the receptor on cell membrane. The approach is sensitive enough to detect antigen-specific B cells at steady state, and can be adapted for any membrane antigen.


Asunto(s)
Antígenos de Superficie/inmunología , Linfocitos B/inmunología , Separación Celular/métodos , Adulto , Anciano , Animales , Antígenos de Superficie/aislamiento & purificación , Autoantígenos/inmunología , Autoantígenos/aislamiento & purificación , Subgrupos de Linfocitos B/inmunología , Línea Celular Tumoral , Células Clonales , Epítopos de Linfocito B/inmunología , Glicoproteínas Hemaglutininas del Virus de la Influenza/inmunología , Humanos , Inmunofenotipificación , Activación de Linfocitos , Ratones , Ratones Endogámicos C57BL , Persona de Mediana Edad , Miastenia Gravis/inmunología , Receptores Colinérgicos/inmunología
15.
Interact J Med Res ; 7(2): e10282, 2018 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-30578181

RESUMEN

BACKGROUND: According to the language expectancy theory and the communication accommodation theory, health information seekers' trust evaluations of Web-based videos are determined by interplays between content and seekers' expectations on vloggers' appropriate language use in specific contexts of Web-based communication. OBJECTIVES: Two investigations focused on differences both between vloggers' language styles and between users' general trust in specific Web-based platforms to investigate how the context of Web-based communication can be characterized (research question, RQ1). Thereafter, we investigated whether information uncertainty, vloggers' language style, and context of Web-based communication affect seekers' trust evaluations of videos (RQ2). METHODS: With a content analysis of 36 health videos from YouTube and Vimeo, we examined the extent of trust-related linguistic characteristics (ie, first-person and second-person pronouns). Additionally, we surveyed participants (n=151) on their trust in YouTube and Moodle (academic Web-based platform; RQ1). In an experiment, further participants (n=124) watched a video about nutrition myths and were asked to evaluate the information credibility, vloggers' trustworthiness, and accommodation of language by vloggers (RQ2). Following a 3 × 2 × 2 mixed design, vloggers' explanations contained unambiguous (confirming or disconfirming) or ambiguous (neither confirming nor disconfirming) evidence on the myths (within factor). Furthermore, vloggers used YouTube-typical language (many first-person pronouns) or formal language (no first-person pronouns), and videos were presented on YouTube or Moodle (between factors). RESULTS: The content analysis revealed that videos on YouTube contained more first-person pronouns than on Vimeo (F1,35=4.64; P=.04; ηp2=0.12), but no more second-person pronouns (F1,35=1.23; P=.23). Furthermore, when asked about their trust in YouTube or Moodle, participants trusted YouTube more than Moodle (t150≤-9.63; all P≤.001). In the experiment, participants evaluated information to be more credible when information contained unambiguous rather than ambiguous evidence (F2,116=9.109; P<.001; ηp2=0.14). Unexpectedly, information credibility did not depend on vloggers' language style or the video platform (F1,117≤2.40; P≥.06). Likewise, video's platform did not affect participants' evaluations of vloggers'trustworthiness (F1,117<0.18; P>.34). However, participants judged vloggers who used a YouTube-typical language as being more benevolent, and their language use as being more appropriate in both video platforms (F1,117≥3.41; P≤.03; ηp2≥0.028). Moreover, participants rated the YouTube-typical (vs formal) language as more appropriate for Moodle, but they did not rate one or the other language style as more appropriate for YouTube (F1,117=5.40; P=.01; ηp2=0.04). CONCLUSIONS: This study shows that among specific Web-based contexts, users' typical language use can differ, as can their trust-related evaluations. In addition, health information seekers seem to be affected by providers' language styles in ways that depend on the Web-based communication context. Accordingly, further investigations that would identify concrete interplays between language style and communication context might help providers to understand whether additional information would help or hurt seekers' ability to accurately evaluate information.

16.
J Med Internet Res ; 20(1): e30, 2018 01 23.
Artículo en Inglés | MEDLINE | ID: mdl-29362212

RESUMEN

BACKGROUND: Online health forums are widely used, but the quality of advice differs as much as the knowledge backgrounds of the audience members who receive the advice. It is important to understand how people judge the information given online. In line with the communication accommodation theory (CAT), online forums represent specific social contexts of communication which can present either accommodative or nonaccommodative language to an audience. Accordingly, use of accommodative or nonaccommodative language might affect people's perceived trust in the communicator. OBJECTIVE: The objective of this study was to investigate how experts who use accommodative (vs nonaccommodative) language are evaluated by passive users of an online forum. METHODS: Participants (n=98) took part in an online experiment and read experts' posts about 10 nutrition myths. Following a 2 x 2 mixed design, experts' posts were written using either low or high amounts of medical technical jargon (MTJ) (within factor) and were directed at different audiences (mainly other medical experts [in a professional forum] vs a user group mainly comprising laypersons [in an advisory forum]) (between factor). Accommodation occurred where experts used high amounts of MTJ to address other medical experts in the professional forum; it also occurred when experts used low amounts of MTJ to address laypersons in the advisory forum. Conversely, nonaccommodation occurred when experts used high amounts of MTJ in the advisory forum and low amounts of MTJ in the professional forum. In each condition, participants evaluated the credibility of the information, the trustworthiness of the experts, and the accommodation by the experts. RESULTS: Overall, participants judged the credibility of information to be higher when experts used MTJ that was accommodative to the designated audience, F1,95=3.10, P=.04, ηp2=.031. In addition, participants judged the experts in professional forums to be more trustworthy than experts in advisory forums (all F1,96≥3.54, P ≤.03, ηp2≥.036). Moreover, participants rated experts who used high amounts of MTJ to have higher competence (F1,96=37.54, P<.001, ηp2=.28], lower integrity (F1,96=10.77, P=.001, ηp2=.101), and lower benevolence (F1,96=9.75, P=.002, ηp2=.092), as well as to have lower perceived accommodation to the audience (all F1,96≥72.17, P<.001, ηp2≥.43) compared with experts who used low MTJ. CONCLUSIONS: To provide health information online that is perceived as credible, experts should consider using similar language as the language used by the addressed audience. As it is often impossible to determine the exact makeup of an online audience, further research might investigate whether having experts explicitly declare which audience they intend to address can help people to more reliably assess an expert's trustworthiness. Furthermore, as people assess information differently depending on the context of online communication, it would be valuable for research to consider other aspects of the context beyond those of the audience.


Asunto(s)
Internet/normas , Telemedicina/normas , Adolescente , Adulto , Comunicación , Comprensión , Femenino , Humanos , Masculino , Persona de Mediana Edad , Percepción , Adulto Joven
17.
Sci Rep ; 7(1): 17448, 2017 12 12.
Artículo en Inglés | MEDLINE | ID: mdl-29234091

RESUMEN

Training can induce cross-modal plasticity in the human cortex. A well-known example of this phenomenon is the recruitment of visual areas for tactile and auditory processing. It remains unclear to what extent such plasticity is associated with changes in anatomy. Here we enrolled 29 sighted adults into a nine-month tactile Braille-reading training, and used voxel-based morphometry and diffusion tensor imaging to describe the resulting anatomical changes. In addition, we collected resting-state fMRI data to relate these changes to functional connectivity between visual and somatosensory-motor cortices. Following Braille-training, we observed substantial grey and white matter reorganization in the anterior part of early visual cortex (peripheral visual field). Moreover, relative to its posterior, foveal part, the peripheral representation of early visual cortex had stronger functional connections to somatosensory and motor cortices even before the onset of training. Previous studies show that the early visual cortex can be functionally recruited for tactile discrimination, including recognition of Braille characters. Our results demonstrate that reorganization in this region induced by tactile training can also be anatomical. This change most likely reflects a strengthening of existing connectivity between the peripheral visual cortex and somatosensory cortices, which suggests a putative mechanism for cross-modal recruitment of visual areas.


Asunto(s)
Ceguera , Aprendizaje , Plasticidad Neuronal , Lectura , Auxiliares Sensoriales , Corteza Visual/diagnóstico por imagen , Adulto , Ceguera/rehabilitación , Femenino , Estudios de Seguimiento , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/fisiología , Humanos , Aprendizaje/fisiología , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/fisiología , Plasticidad Neuronal/fisiología , Tamaño de los Órganos , Descanso , Percepción del Tacto/fisiología , Corteza Visual/fisiología , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/fisiología , Adulto Joven
19.
Proc Natl Acad Sci U S A ; 114(4): E600-E609, 2017 01 24.
Artículo en Inglés | MEDLINE | ID: mdl-28069964

RESUMEN

The principles that guide large-scale cortical reorganization remain unclear. In the blind, several visual regions preserve their task specificity; ventral visual areas, for example, become engaged in auditory and tactile object-recognition tasks. It remains open whether task-specific reorganization is unique to the visual cortex or, alternatively, whether this kind of plasticity is a general principle applying to other cortical areas. Auditory areas can become recruited for visual and tactile input in the deaf. Although nonhuman data suggest that this reorganization might be task specific, human evidence has been lacking. Here we enrolled 15 deaf and 15 hearing adults into an functional MRI experiment during which they discriminated between temporally complex sequences of stimuli (rhythms). Both deaf and hearing subjects performed the task visually, in the central visual field. In addition, hearing subjects performed the same task in the auditory modality. We found that the visual task robustly activated the auditory cortex in deaf subjects, peaking in the posterior-lateral part of high-level auditory areas. This activation pattern was strikingly similar to the pattern found in hearing subjects performing the auditory version of the task. Although performing the visual task in deaf subjects induced an increase in functional connectivity between the auditory cortex and the dorsal visual cortex, no such effect was found in hearing subjects. We conclude that in deaf humans the high-level auditory cortex switches its input modality from sound to vision but preserves its task-specific activation pattern independent of input modality. Task-specific reorganization thus might be a general principle that guides cortical plasticity in the brain.


Asunto(s)
Corteza Auditiva/fisiología , Sordera/fisiopatología , Estimulación Acústica , Adulto , Corteza Auditiva/diagnóstico por imagen , Sordera/diagnóstico por imagen , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Estimulación Luminosa , Adulto Joven
20.
Proc Natl Acad Sci U S A ; 114(4): 734-739, 2017 01 24.
Artículo en Inglés | MEDLINE | ID: mdl-28057865

RESUMEN

Autoantibodies against myelin oligodendrocyte glycoprotein (MOG) are associated with autoimmune central nervous system diseases like acute disseminated encephalomyelitis (ADEM). For ADEM, it is speculated that a preceding infection is the trigger of the autoimmune response, but the mechanism connecting the infection to the production of MOG antibodies remains a mystery. We reasoned that the ability of B cells to capture cognate antigen from cell membranes, along with small quantities of coexpressed "bystander" antigens, might enable B-cell escape from tolerance. We tested this hypothesis using influenza hemagglutinin as a model viral antigen and transgenic, MOG-specific B cells. Using flow cytometry and live and fixed cell microscopy, we show that MOG-specific B cells take up large amounts of MOG from cell membranes. Uptake of the antigen from the membrane leads to a strong activation of the capturing B cell. When influenza hemagglutinin is also present in the membrane of the target cell, it can be cocaptured with MOG by MOG-specific B cells via the B-cell receptor. Hemagglutinin and MOG are both presented to T cells, which in turn are activated and proliferate. As a consequence, MOG-specific B cells get help from hemagglutinin-specific T cells to produce anti-MOG antibodies. In vivo, the transfer of MOG-specific B cells into recipient mice after the cocapture of MOG and hemagglutinin leads to the production of class-switched anti-MOG antibodies, dependent on the presence of hemagglutinin-specific T cells. This mechanism offers a link between infection and autoimmunity.


Asunto(s)
Antígenos Virales/inmunología , Autoantígenos/inmunología , Linfocitos B/inmunología , Animales , Autoanticuerpos/inmunología , Autoinmunidad/inmunología , Línea Celular , Membrana Celular/inmunología , Células HEK293 , Glicoproteínas Hemaglutininas del Virus de la Influenza/inmunología , Humanos , Ratones , Ratones Endogámicos C57BL , Glicoproteína Mielina-Oligodendrócito/inmunología , Receptores de Antígenos de Linfocitos B/inmunología , Linfocitos T/inmunología
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