A proposal for the assessment of replication of effects in single-case experimental designs

In science in general and in the context of single-case experimental designs, replication of the effects of the intervention within and/or across participants or experiments is crucial for establishing causality and for assessing the generality of the intervention effect. Specific developments and proposals for assessing whether an effect has been replicated or not (or to what extent) are scarce, in the general context of behavioral sciences, and practically null in the singlecase experimental designs context. We propose an extension of the modified Brinley plot for assessing how many of the effects replicate. To make this assessment possible, a definition of replication is suggested, on the basis of expert judgment, rather than on statistical criteria. The definition of replication and its graphical representation are justified, presenting their strengths and limitations, and illustrated with real data. A user-friendly software is made available for obtaining automatically the graphical representation

Relation between executive functions and screen time exposure in under 6 year-olds: a meta-analysis

Some previous research works have reported potential benefits of screen media use in children aged under 6 years, and others have evidenced that screen media use might be particularly detrimental. To our knowledge, this is the first study to provide the first meta-analytic synthesis of existing research on the relation between overall screen time use and EFs. To address this issue, the current meta-analysis aimed to review the relations between overall screen time and EF in infants, toddlers and preschoolers. A systematic search was done on Web of Science and EBSCO to identify the eligible studies published until January 2023. Fifteen manuscripts with 6922 participants aged 0–6 years were included, and yielded 44 effect sizes. Three-level models were carried out, and the following study characteristics were tested as potential moderators: mean age, percentage of females, EF type, and whether exposure was active or passive. There was no statistically significant association in the relation between overall time use and EF or in the chosen moderators. Nevertheless, the study highlights the need to consider other contextual-related and development-related factors to determine the overall screen time use effect on EF in children

Empirical Evidence of the Metacognitive Model of Rumination and Depression in Clinical and Nonclinical Samples: A Systematic Review and Meta-Analysis

Rumination is considered a cognitive vulnerability factor in the development and maintenance of depression. The metacognitive model of rumination and depression suggests that the development of rumination and its association with depression partly depends on metacognitive beliefs. Two metacognitive beliefs about rumination have been identified: positive beliefs about its utility and negative beliefs about the uncontrollability and its negative social consequences. We conducted a systematic review and meta-analysis aimed: (1) to analyze the associations between metacognitive beliefs and rumination and depression; (2) to test the metacognitive model, using a Two-Stage Structural Equation Modeling approach (TSSEM). Literature search retrieved 41 studies. These 41 studies (N = 10,607) were included in the narrative synthesis and meta-analysis, and 16 studies (N = 4477) were comprised for the TSSEM. Results indicated metacognitive beliefs are associated with rumination and depression. Measures on metacognitive beliefs about rumination indicated that positive beliefs showed moderate associations with rumination (r = 0.50), and low with depression (r = 0.27); whereas negative beliefs showed moderate associations with both rumination (r = 0.46) and depression (r = 0.49). These results were consistent across studies using different instruments to measure metacognitive beliefs, and in both clinical and nonclinical samples. Moreover, results of the TSSEM analyses showed that the metacognitive model had a good fit. In sum, our results are in line with the metacognitive model of rumination and depression, highlighting that metacognitive beliefs are relevant factors to understand why people ruminate and get depressed. Future directions and clinical implications are discussed

Does technology-based interventions in psychosis improved functioning and quality of life? A systematic review and meta-analysis

Introduction: Technology-based interventions (TBIs), including computer and Internet-based interventions, mobile interventions, health applications, social media interventions, and interventions using technological devices, could become a useful, effective, accessible, and cost-effective approach (Berry et al., 2016; Firth, 2016) to complement conventional interventions for psychosi

Bovine Spongiform Encephalopathy Induces Misfolding of Alleged Prion-Resistant Species Cellular Prion Protein without Altering Its Pathobiological Features

Bovine spongiform encephalopathy (BSE) prions were responsible for an unforeseen epizootic in cattle which had a vast social, economic, and public health impact. This was primarily because BSE prions were found to be transmissible to humans. Other species were also susceptible to BSE either by natural infection (e.g., felids, caprids) or in experimental settings (e.g., sheep, mice). However, certain species closely related to humans, such as canids and leporids, were apparently resistant to BSE. In vitro prion amplification techniques (saPMCA) were used to successfully misfold the cellular prion protein (PrPc) of these allegedly resistant species into a BSE-type prion protein. The biochemical and biological properties of the new prions generated in vitro after seeding rabbit and dog brain homogenates with classical BSE were studied. Pathobiological features of the resultant prion strains were determined after their inoculation into transgenic mice expressing bovine andhumanPrPC. Strain characteristics of the in vitro-adapted rabbit and dog BSE agent remained invariable with respect to the original cattle BSE prion, suggesting that the naturally low susceptibility of rabbits and dogs to prion infections should not alter their zoonotic potential if these animals became infected with BSE. This study provides a sound basis for risk assessment regarding prion diseases in purportedly resistant species

Transgenic Mouse Bioassay : Evidence That Rabbits Are Susceptible to a Variety of Prion Isolates

Interspecies transmission of prions is a well-established phenomenon, both experimentally and under field conditions. Upon passage through new hosts, prion strains have proven their capacity to change their properties and this is a source of strain diversity which needs to be considered when assessing the potential risks associated with consumption of prion contaminated protein sources. Rabbits were considered for decades to be a prion resistant species until proven otherwise recently. To determine the extent of rabbit susceptibility to prions and to assess the effects of passage of different prion strains through this species a transgenic mouse model overexpressing rabbit PrPC was developed (TgRab). Intracerebral challenges with prion strains originating from a variety of species including field isolates (ovine SSBP/1 scrapie, Nor98- scrapie; cattle BSE, BSE-L and cervid CWD), experimental murine strains (ME7 and RML) and experimentally obtained ruminant (sheepBSE) and rabbit (de novo NZW) strains were performed. On first passage TgRab were susceptible to the majority of prions (Cattle BSE, SheepBSE, BSE-L, de novo NZW, ME7 and RML) tested with the exception of SSBP/1 scrapie, CWD and Nor98 scrapie. Furthermore, TgRab were capable of propagating strain-specific features such as differences in incubation periods, histological brain lesions, abnormal prion (PrPd) deposition profiles and proteinase-K (PK) resistant western blotting band patterns. Our results confirm previous studies proving that rabbits are not resistant to prion infection and show for the first time that rabbits are susceptible to PrPd originating in a number of other species. This should be taken into account when choosing protein sources to feed rabbits

Dogs are resistant to prion infection, due to the presence of aspartic or glutamic acid at position 163 of their prion protein

Unlike other species, prion disease has never been described in dogs even though they were similarly exposed to the bovine spongiform encephalopathy (BSE) agent. This resistance prompted a thorough analysis of the canine PRNP gene and the presence of a negatively charged amino acid residue in position 163 was readily identified as potentially fundamental as it differed from all known susceptible species. In the present study, the first transgenic mouse model expressing dog prion protein (PrP) was generated and challenged intracerebrally with a panel of prion isolates, none of which could infect them. The brains of these mice were subjected to in vitro prion amplification and failed to find even minimal amounts of misfolded prions providing definitive experimental evidence that dogs are resistant to prion disease. Subsequently, a second transgenic model was generated in which aspartic acid in position 163 was substituted for asparagine (the most common in prion susceptible species) resulting in susceptibility to BSE‐derived isolates. These findings strongly support the hypothesis that the amino acid residue at position 163 of canine cellular prion protein (PrPC) is a major determinant of the exceptional resistance of the canidae family to prion infection and establish this as a promising therapeutic target for prion diseases.MINECO/FEDER. Grant Numbers: AGL2015‐65046‐C2‐1‐R, AGL2008‐05296‐C02 Interreg. Grant Number: POCTEFA EFA148/1

Characterization of mesenchymal stem cells in sheep naturally infected with scrapie

Mesenchymal stem cells (MSCs) can be infected with prions and have been proposed as in vitro cell-based models for prion replication. In addition, autologous MSCs are of interest for cell therapy in neurodegenerative diseases. To the best of our knowledge, the effect of prion diseases on the characteristics of these cells has never been investigated. Here, we analysed the properties of MSCs obtained from bone marrow (BM-MSCs) and peripheral blood (PB-MSCs) of sheep naturally infected with scrapie — a large mammal model for the study of prion diseases. After three passages of expansion, MSCs derived from scrapie animals displayed similar adipogenic, chondrogenic and osteogenic differentiation ability as cells from healthy controls, although a subtle decrease in the proliferation potential was observed. Exceptionally, mesenchymal markers such as CD29 were significantly upregulated at the transcript level compared with controls. Scrapie MSCs were able to transdifferentiate into neuron-like cells, but displayed lower levels of neurogenic markers at basal conditions, which could limit this potential. The expression levels of cellular prion protein (PrPC) were highly variable between cultures, and no significant differences were observed between control and scrapie-derived MSCs. However, during neurogenic differentiation the expression of PrPC was upregulated in MSCs. This characteristic could be useful for developing in vitro models for prion replication. Despite the infectivity reported for MSCs obtained from scrapie-infected mice and Creutzfeldt–Jakob disease patients, protein misfolding cyclic amplification did not detect PrPSc in BM- or PB-MSCs from scrapie-infected sheep, which limits their use for in vivo diagnosis for scrapie

An amino acid substitution found in animals with low susceptibility to prion diseases confers a protective dominant-negative effect in prion-infected transgenic mice

While prion diseases have been described in numerous species, some, including those of the Canidae family, appear to show resistance or reduced susceptibility. A better understanding of the factors underlying prion susceptibility is crucial for the development of effective treatment and control measures. We recently demonstrated resistance to prion infection in mice overexpressing a mutated prion protein (PrP) carrying a specific amino acid substitution characteristic of canids. Here, we show that coexpression of this mutated PrP and wild-type mouse PrP in transgenic mice inoculated with different mouse-adapted prion strains (22 L, ME7, RML, and 301C) significantly increases survival times (by 45 to 113%). These data indicate that this amino acid substitution confers a dominant-negative effect on PrP, attenuating the conversion of PrPC to PrPSc and delaying disease onset without altering the neuropathological properties of the prion strains. Taken together, these findings have important implications for the development of new treatment approaches for prion diseases based on dominant-negative proteins

Leer en comunidad: Creación y desarrollo de clubes de lectura dentro y fuera de la Universidad

Depto. de Lengua Española y Teoría de la LiteraturaFac. de FilologíaFALSEsubmitte