Induced pluripotent stem cell line (INSAi001-A) from a Gaucher disease type 3 patient compound heterozygote for mutations in the GBA1 gene

Gaucher Disease (GD) type 3 is a neurological form of a multisystemic autosomal recessive disorder belonging to the group of lysosomal storage diseases. Causal mutations in the glucocerebrosidase 1 (GBA1) commonly lead to abnormal protein and GD, heterozygosity is a genetic risk factor for Parkinson's disease. This work describes the use of a non-integrative approach using Sendai Virus delivery to establish induced Pluripotent Stem Cells (iPSCs) from fibroblasts from a GD type 3 patient. Differentiation of iPSCs can be employed to generate a variety of complex cell types with a high degree of genetic complexity that would otherwise be unattainable.Funding Agency Portuguese Foundation for Science and Technology PTDC/BIM-MEC/4762/2014info:eu-repo/semantics/publishedVersio

Juntando mais peças ao puzzle do léxico da LPG: três estudos pilotos

The main goal of this article is to present several pieces of the “puzzle” concerning Portuguese Sign Language (LGP) lexicon – polissemy, linguistic specialization of forms and the sign’s history throughout time –, thus demonstrating how these pieces fit into the linguistic mechanism of human creativity and the dynamic evolution of languages, two privileged factors in cultural expression. O principal objectivo deste artigo foi apresentar as várias peças que compõem o puzzle do léxico da Língua Gestual Portuguesa (LGP) – a polissemia, a especialização linguística das formas e a história dos gestos através do tempo – demonstrando como essas peças se emolduram no mecanismo linguístico da criatividade humana e da evolução dinâmica das línguas, enquanto factores privilegiados de expressão cultural. &nbsp

Efficient IDUA Gene Mutation Detection with Combined Use of dHPLC and Dried Blood Samples

DR and AJD were FCT research grantees (PIC/IC/82822/2007)Development of a simple mutation directed method in order to allow lowering the cost of mutation testing using an easily obtainable biological material. Assessment of the feasibility of such method was tested using a GC-rich amplicon. A method of denaturing high-performance liquid chromatography (dHPLC) was improved and implemented as a technique for the detection of variants in exon 9 of the IDUA gene. The optimized method was tested in 500 genomic DNA samples obtained from dried blood spots (DBS). With this dHPLC approach it was possible to detect different variants, including the common p.Trp402Ter mutation in the IDUA gene. The high GC content did not interfere with the resolution and reliability of this technique, and discrimination of G-C transversions was also achieved. This PCR-based dHPLC method proved to be a rapid, a sensitive, and an excellent option for screening numerous samples obtained from DBS. Furthermore, it resulted in the consistent detection of clearly distinguishable profiles of the common p.Trp402Ter IDUA mutation with an advantageous balance of cost and technical requirements.FCT [2009-2013

The contribution of the user experiences goals for designing better cobots: a systematic literature review

Collaborative robots are an indispensable element of both industry 4.0 and industry 5.0, the latter of which gives special emphasis to the human facet of the human-robot collaboration. To facilitate such an interaction, attention should be given to the design of the cobot, including its interface, which enables communication with the user. Programming through the interface and performing a task with the robotic device are responsible for the user experience (UX), which comprises both pragmatic and hedonic aspects. In order to design the most positive experience for users, their perspectives must be considered, which is achieved through the identification of UX goals. In this respect, a systematic review was conducted to revise the UX goals present in the literature. The following seven UX goals were identified: safety, relationship, usability, inspiration, flexibility, efficiency, and accomplishment. These findings represent the first systematic categorization of UX goals for the specific design of cobots, that should empirically be tested.info:eu-repo/semantics/publishedVersio

Psychoactive Substances of Natural Origin: Toxicological Aspects, Therapeutic Properties and Analysis in Biological Samples

The consumption of new psychoactive substances (NPSs) has been increasing, and this problem affects several countries worldwide. There is a class of NPSs of natural origin, consisting of plants and fungi, which have a wide range of alkaloids, responsible for causing relaxing, stimulating or hallucinogenic effects. The consumption of some of these substances is prompted by religious beliefs and cultural reasons, making the legislation very variable or even ambiguous. However, the abusive consumption of these substances can present an enormous risk to the health of the individuals, since their metabolism and effects are not yet fully known. Additionally, NPSs are widely spread over the internet, and their appearance is very fast, which requires the development of sophisticated analytical methodologies, capable of detecting these compounds. Thus, the objective of this work is to review the toxicological aspects, traditional use/therapeutic potential and the analytical methods developed in biological matrices in twelve plant specimens (Areca catechu, Argyreia nervosa, Ayahuasca, Catha edulis, Datura stramonium, Lophophora williamsii, Mandragora officinarum, Mitragyna speciosa, Piper methysticum Forst, Psilocybe, Salvia divinorum and Tabernanthe iboga).info:eu-repo/semantics/publishedVersio

In silico analysis of missense mutations as a first step in functional studies: examples from two sphingolipidoses

Free PMC Article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6275066/Note: Where it reads BBB-BMD/6301, should be PTDC/BIM-MEC/4762/2014. Erro de edição, tendo sido solicitado correção.In order to delineate a better approach to functional studies, we have selected 23 missense mutations distributed in different domains of two lysosomal enzymes, to be studied by in silico analysis. In silico analysis of mutations relies on computational modeling to predict their effects. Various computational platforms are currently available to check the probable causality of mutations encountered in patients at the protein and at the RNA levels. In this work we used four different platforms freely available online (Protein Variation Effect Analyzer- PROVEAN, PolyPhen-2, Swiss-model Expert Protein Analysis System-ExPASy, and SNAP2) to check amino acid substitutions and their effect at the protein level. The existence of functional studies, regarding the amino acid substitutions, led to the selection of the distinct protein mutants. Functional data were used to compare the results obtained with different bioinformatics tools. With the advent of next-generation sequencing, it is not feasible to carry out functional tests in all the variants detected. In silico analysis seems to be useful for the delineation of which mutants are worth studying through functional studies. Therefore, prediction of the mutation impact at the protein level, applying computational analysis, confers the means to rapidly provide a prognosis value to genotyping results, making it potentially valuable for patient care as well as research purposes. The present work points to the need to carry out functional studies in mutations that might look neutral. Moreover, it should be noted that single nucleotide polymorphisms (SNPs), occurring in coding and non-coding regions, may lead to RNA alterations and should be systematically verified. Functional studies can gain from a preliminary multi-step approach, such as the one proposed here.Financial support was received from the Portuguese Foundation of Science and Technology (FCT), project PTDC/BIM-MEC/4762/2014 (PI-O.A.) Diogo Ribeiro and Luciana Moreira were grant recipients from FCT under the same project. Ana Duarte was a PhD student with grant a FCTSFRH/BD/118009/2016.info:eu-repo/semantics/publishedVersio

Evaluation of the In Vitro Wound-Healing Potential of Ayahuasca

yahuasca is an Amazonian drink, which contains β-carboline alkaloids and N,N- dimethyltryptamine. The aim of this study was to evaluate the healing potential of decoctions of a commercial mixture, four individual plants and four mixtures of two plants used in the ayahuasca preparation. Thus, the cytotoxic potential of the samples was evaluated and a wound-healing assay was performed with a NHDF cell line. Subsequently, a parallel artificial membrane permeability assay was also performed, to verify if any psychoactive compound could be absorbed by skin fibroblasts. The integrity and permeability of the cell layer were also evaluated, using the transepithelial electrical resistance assay and Lucifer yellow permeability assay, respectively. The compounds absorbed by the cell layer were quantified by high-performance liquid chromatography coupled to a diode array detector. The results showed that only one sample showed cytotoxicity and all the others promoted the migration of skin fibroblasts. Additionally, it was also verified that β-carbolynic alkaloids and N,N-dimethyltriptamine were not absorbed by the cell layer, and in general, did not interfere with its permeability and integrity. To the best of our knowledge, this is the first study where ayahuasca’s wound-healing potential was evaluated.info:eu-repo/semantics/publishedVersio

A Systematic Review on the Therapeutic Effects of Ayahuasca

Traditional therapies, resorting to the use of plants, have acquired a great demand over the years, both for economic reasons and the preference for natural treatments. Some studies suggest that ayahuasca may have beneficial properties in treating some physical and psychological imbalances. Thus, we carried out a systematic review of studies published up to December 2022, where these themes were addressed. The search was carried out in the PubMed database, and only studies written in English and published in peer-reviewed journals were included. Thus, 228 publications were identified, of which 66 were included in the present study. The reviewed studies suggest that ayahuasca may have beneficial effects on various physical and psychological conditions, namely in the treatment of depression, anxiety and various diseases of the neurobiological system, as well as anti-inflammatory and antimicrobial properties, demonstrating its therapeutic potential. The number of studies that address this issue has also been growing, demonstrating interest in the search for alternative treatments. However, to the best of our knowledge, this is the first systematic review where all the findings of therapeutic effects associated with the consumption of ayahuasca are reviewed.info:eu-repo/semantics/publishedVersio

Enhancing cobot design through user experience goals: An investigation of human–robot collaboration in picking tasks

The use of collaborative robots in industries is growing rapidly. To ensure the successful implementation of these devices, it is essential to consider the user experience (UX) during their design process. This study is aimed at testing the UX goals that emerge when users interact with a collaborative robot during the programming and collaborating phases. A framework on UX goals will be tested, in the geographical context of Portugal. For that, an experimental setup was introduced in the form of a laboratory case study in which the human–robot collaboration (HRC) was evaluated by the combination of both quantitative (applying the User Experience Questionnaire [UEQ]) and qualitative (semistructured interviews) metrics. The sample was constituted by 19 university students. The quantitative approach showed positive overall ratings for the programming phase UX, with attractiveness having the highest average value (M = 2 21; SD = 0 59) and dependability the lowest (M = 1 64; SD = 0 65). For the collaboration phase, all UX ratings were positive, with attractiveness having the highest average value (M = 2 46; SD = 0 78) and efficiency the lowest (M = 1 93; SD = 0 77). Only perspicuity showed significant differences between the two phases (t 18 = −4 335, p = 0 002). The qualitative approach, at the light of the framework used, showed that efficiency, inspiration, and usability are the most mentioned UX goals emerging from the content analysis. These findings enhance manufacturing workers’ well-being by improving cobot design in organizations.info:eu-repo/semantics/publishedVersio

β-lactam dosing in critical patients: a narrative review of optimal efficacy and the prevention of resistance and toxicity

© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).Antimicrobial prescription in critically ill patients represents a complex challenge due to the difficult balance between infection treatment and toxicity prevention. Underexposure to antibiotics and therapeutic failure or, conversely, drug overexposure and toxicity may both contribute to a worse prognosis. Moreover, changes in organ perfusion and dysfunction often lead to unpredictable pharmacokinetics. In critically ill patients, interindividual and intraindividual real-time β-lactam antibiotic dose adjustments according to the patient's condition are critical. The continuous infusion of β-lactams and the therapeutic monitoring of their concentration have both been proposed to improve their efficacy, but strong data to support their use are still lacking. The knowledge of the pharmacokinetic/pharmacodynamic targets is poor and is mostly based on observational data. In patients with renal or hepatic failure, selecting the right dose is even more tricky due to changes in drug clearance, distribution, and the use of extracorporeal circuits. Intermittent usage may further increase the dosing conundrum. Recent data have emerged linking overexposure to β-lactams to central nervous system toxicity, mitochondrial recovery delay, and microbiome changes. In addition, it is well recognized that β-lactam exposure facilitates resistance selection and that correct dosing can help to overcome it. In this review, we discuss recent data regarding real-time β-lactam antibiotic dose adjustment, options in special populations, and the impacts on mitochondria and the microbiome.info:eu-repo/semantics/publishedVersio