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1.
Photochem Photobiol Sci ; 23(5): 823-837, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38568410

RESUMO

Titanium dioxide (TiO2) is a well-known material for its biomedical applications, among which its implementation as a photosensitizer in photodynamic therapy has attracted considerable interest due to its photocatalytic properties, biocompatibility, high chemical stability, and low toxicity. However, the photoactivation of TiO2 requires ultraviolet light, which may lead to cell mutation and consequently cancer. To address these challenges, recent research has focused on the incorporation of metal dopants into the TiO2 lattice to shift the band gap to lower energies by introducing allowed energy states within the band gap, thus ensuring the harnessing of visible light. This study presents the synthesis, characterization, and application of TiO2 nanoparticles (NPs) in their undoped, doped, and co-doped forms for antimicrobial photodynamic therapy (APDT) against Candida albicans. Blue light with a wavelength of 450 nm was used, with doses ranging from 20 to 60 J/cm2 and an NP concentration of 500 µg/ml. It was observed that doping TiO2 with Cu, Fe, Ag ions, and co-doping Cu:Fe into the TiO2 nanostructure enhanced the visible light photoactivity of TiO2 NPs. Experimental studies were done to investigate the effects of different ions doped into the TiO2 crystal lattice on their structural, optical, morphological, and chemical composition for APDT applications. In particular, Ag-doped TiO2 emerged as the best candidate, achieving 90-100% eradication of C. albicans.


Assuntos
Antifúngicos , Candida albicans , Luz , Nanopartículas , Titânio , Titânio/química , Titânio/farmacologia , Antifúngicos/farmacologia , Antifúngicos/química , Antifúngicos/síntese química , Candida albicans/efeitos dos fármacos , Nanopartículas/química , Testes de Sensibilidade Microbiana , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/síntese química , Fotoquimioterapia
2.
Fish Shellfish Immunol ; 87: 136-143, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30610930

RESUMO

In aquaculture, fighting infectious diseases is a necessity. This study measured the immuno-stimulating effect of live macroalgae consumption on Litopenaeus vannamei against Vibrio parahaemolyticus and WSSV infection in two independent bioassays. Shrimps and macroalgae were cultivated in a co-culture with two species of macroalgae separately (Gracilaria vermiculophylla and Dictyota dichotoma), and later, shrimp were infected with V. parahaemolyticus. In another bioassay, shrimp and macroalgae (G. vermiculophylla, D. dichotoma and Ulva lactuca) were grown and subsequently infected with WSSV. For both bioassays, survival after 120 h was determined, the total hemocyte count (TCH) was measured and the activity of superoxide dismutase (SOD) and catalase (CAT) in tissue were measured. The results indicate that the use of macroalgae in co-culture with L. vannamei provides a nutritional benefit that achieves higher growth than the control organisms, as well as improvements of the ammonium concentration and immune response after infection with V. parahaemolyticus and WSSV. A better immune response was obtained in organisms cultured with macroalgae in both bioassays at a ratio of 1.6-1.9 for organisms infected with bacteria and 1.4 to 1.6 times for organisms infected with the virus. In turn, the enzymatic activity of SOD and CAT were higher in the treated organisms relative to the controls in both experiments.


Assuntos
Penaeidae/microbiologia , Penaeidae/virologia , Vibrio parahaemolyticus/imunologia , Vírus da Síndrome da Mancha Branca 1/imunologia , Animais , Aquicultura , Gracilaria/crescimento & desenvolvimento , Penaeidae/crescimento & desenvolvimento , Phaeophyceae/crescimento & desenvolvimento , Ulva/crescimento & desenvolvimento
3.
Bioorg Med Chem ; 27(17): 3788-3796, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31320211

RESUMO

Novel analogs of the allosteric, biased PAR1 ligand ML161 (parmodulin 2, PM2) were prepared in order to identify potential anti-thrombotic and anti-inflammatory compounds of the parmodulin class with improved properties. Investigations of structure-activity relationships of the western portion of the 1,3-diaminobenzene scaffold were performed using an intracellular calcium mobilization assay with endothelial cells, and several heterocycles were identified that inhibited PAR1 at sub-micromolar concentrations. The oxazole NRD-21 was profiled in additional detail, and it was confirmed to act as a selective, reversible, negative allosteric modulator of PAR1. In addition to inhibiting human platelet aggregation, it showed superior anti-inflammatory activity to ML161 in a qPCR assay measuring the expression of tissue factor in response to the cytokine TNF-alpha in endothelial cells. Additionally, NRD-21 is much more plasma stable than ML161, and is a promising lead compound for the parmodulin class for anti-thrombotic and anti-inflammatory indications.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Oxazóis/farmacologia , Receptor PAR-1/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Regulação Alostérica/efeitos dos fármacos , Anti-Inflamatórios não Esteroides/química , Relação Dose-Resposta a Droga , Estabilidade de Medicamentos , Humanos , Ligantes , Estrutura Molecular , Oxazóis/síntese química , Oxazóis/química , Agregação Plaquetária/efeitos dos fármacos , Receptor PAR-1/metabolismo , Relação Estrutura-Atividade
4.
Bioorg Med Chem ; 26(9): 2514-2529, 2018 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-29685684

RESUMO

Several classes of ligands for Protease-Activated Receptors (PARs) have shown impressive anti-inflammatory and cytoprotective activities, including PAR2 antagonists and the PAR1-targeting parmodulins. In order to support medicinal chemistry studies with hundreds of compounds and to perform detailed mode-of-action studies, it became important to develop a reliable PAR assay that is operational with endothelial cells, which mediate the cytoprotective effects of interest. We report a detailed protocol for an intracellular calcium mobilization assay with adherent endothelial cells in multiwell plates that was used to study a number of known and new PAR1 and PAR2 ligands, including an alkynylated version of the PAR1 antagonist RWJ-58259 that is suitable for the preparation of tagged or conjugate compounds. Using the cell line EA.hy926, it was necessary to perform media exchanges with automated liquid handling equipment in order to obtain optimal and reproducible antagonist concentration-response curves. The assay is also suitable for study of PAR2 ligands; a peptide antagonist reported by Fairlie was synthesized and found to inhibit PAR2 in a manner consistent with reports using epithelial cells. The assay was used to confirm that vorapaxar acts as an irreversible antagonist of PAR1 in endothelium, and parmodulin 2 (ML161) and the related parmodulin RR-90 were found to inhibit PAR1 reversibly, in a manner consistent with negative allosteric modulation.


Assuntos
Benzamidas/farmacologia , Cálcio/metabolismo , Fenilenodiaminas/farmacologia , Receptor PAR-1/antagonistas & inibidores , Receptor PAR-2/antagonistas & inibidores , Tecnologia Farmacêutica/métodos , Regulação Alostérica , Benzamidas/síntese química , Linhagem Celular , Células Endoteliais/metabolismo , Humanos , Iminas/farmacologia , Indazóis/síntese química , Indazóis/farmacologia , Lactonas/farmacologia , Ligantes , Oligopeptídeos/síntese química , Oligopeptídeos/farmacologia , Fenilenodiaminas/síntese química , Piridinas/farmacologia , Receptor PAR-1/agonistas , Receptor PAR-2/agonistas , Ureia/análogos & derivados , Ureia/síntese química , Ureia/farmacologia
5.
Rev Chil Pediatr ; 88(1): 92-99, 2017 Feb.
Artigo em Espanhol | MEDLINE | ID: mdl-28288228

RESUMO

Duchenne muscular dystrophy (DMD) and Spinal muscular atrophy (SMA) causes significant disability and progressive functional impairment. Readily available instruments that assess functionality, especially in advanced stages of the disease, are required to monitor the progress of the disease and the impact of therapeutic interventions. OBJECTIVE: To describe the development of a scale to evaluate upper limb function (UL) in patients with DMD and SMA, and describe its validation process, which includes self-training for evaluators. PATIENTS AND METHOD: The development of the scale included a review of published scales, an exploratory application of a pilot scale in healthy children and those with DMD, self-training of evaluators in applying the scale using a handbook and video tutorial, and assessment of a group of children with DMD and SMA using the final scale. Reliability was assessed using Cronbach and Kendall concordance and with intra and inter-rater test-retest, and validity with concordance and factorial analysis. RESULTS: A high level of reliability was observed, with high internal consistency (Cronbach a = 0.97), and inter-rater (Kendall W = 0.96) and intra-rater concordance (r = 0.97 to 0.99). The validity was demonstrated by the absence of significant differences between results by different evaluators with an expert evaluator (F = 0.023, p > .5), and by the factor analysis that showed that four factors account for 85.44% of total variance. CONCLUSIONS: This scale is a reliable and valid tool for assessing UL functionality in children with DMD and SMA. It is also easily implementable due to the possibility of self-training and the use of simple and inexpensive materials.


Assuntos
Avaliação da Deficiência , Atrofia Muscular Espinal/fisiopatologia , Distrofia Muscular de Duchenne/fisiopatologia , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Progressão da Doença , Análise Fatorial , Feminino , Humanos , Masculino , Variações Dependentes do Observador , Projetos Piloto , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Extremidade Superior
6.
Front Psychol ; 14: 1090710, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36814660

RESUMO

Learning to read for children with Down syndrome is relevant because of the impact this ability has on learning and the development of autonomy. Previous research has described reading development in this population, but it is not clear if the process and precursors are the same in a transparent language like Spanish. This study explores performance in a set of precursors (phonological awareness, visual recognition, vocabulary, letter knowledge and verbal reasoning) in 42 children with Down syndrome between 6:0 and 10:11 years. We hypothesized that the participants would have a lower performance than previously reported with children with typical development, particularly in tasks of phonological awareness, because the method for reading instruction in Chile with this population is usually the global method. Our results show that the precursors improve with age, that there are differences in performance between the skills assessed, and the ceiling effect was not observed as would be expected for children with typical development for the abilities assessed at these ages, which suggests that in the children assessed the precursors are not consolidated at these ages. These results suggest that the stimulation of phonological awareness and other reading precursors in children with Down syndrome is important for reading development.

7.
J Intell ; 10(4)2022 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-36547512

RESUMO

Executive functions are psychological processes of great importance for proper functioning in various areas of human development, including academic performance. For this reason, from both clinical and educational perspectives, there is great interest in how they are assessed. This article describes the development and standardization process of Yellow-Red, an instrument for directly assessing executive functions in children between 6 and 11 years of age in a playful format using digital support. The test was based on a three-factor model of executive functioning: inhibition, working memory, and cognitive flexibility. Yellow-Red comprises six subtests: cognitive inhibition, behavioral inhibition, auditory working memory, visual working memory, cognitive flexibility, and a global assessment test of executive functions. The test was administered to 245 boys and girls between 6 and 11 years of age. Along with the Yellow-Red subtests, gold standard tests were applied for each of the executive functions assessed. The test's psychometric properties are powerful in both reliability and validity evidence. The reliability indices are all greater than 0.8. As evidence of convergent validity, correlations were established between the tests, and the tests considered gold standards. All correlations were significant, with values ranging between 0.42 and 0.73. On the other hand, the factor structure of the test was analyzed using confirmatory factor analysis. Although it is possible to demonstrate the progressive differentiation of the factor structure with age, it was only possible to find two factors at older ages, one for inhibition/flexibility and one for working memory.

8.
Sch Psychol ; 37(1): 85-96, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35025592

RESUMO

This study investigated the repercussions of coronavirus disease (COVID-19) and the subsequent quarantine on the emotional well-being of children in their initial years of formal schooling, with particular emphasis on children with special educational needs (SEN) and children from high and low socioeconomic statuses (SES). This longitudinal study employed the Child Behavior Checklist for ages 6-18 (CBCL) completed by the students' guardians at least once during 2018-2019 and again during 2020. The results showed differences in internalizing and externalizing problems after 8 months of quarantine and a significant increase in students fitting clinical or borderline categories given by the CBCL itself. The results are described in detail for four groups considering the combination of SEN and SES characteristics, showing the importance of their intersectionality, especially between low SES and SEN. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Assuntos
COVID-19 , Pandemias , Adolescente , Criança , Emoções , Humanos , Estudos Longitudinais , SARS-CoV-2
9.
Dement Neuropsychol ; 16(1): 69-78, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35719260

RESUMO

The Frontal Assessment Battery (FAB) is a screening test that measures executive functions. Although this instrument has been validated in several countries, its diagnostic utility in a Chilean population has not been studied yet. Objectives: This study aimed to (1) adapt FAB in a Chilean population; (2) study the psychometric properties of the FAB in a Chilean population; (3) assess the sociodemographic influence in the performance of the FAB in a sample of healthy controls (HC); and (4) develop normative data for this healthy group. Methods: A HC (n=344) and a group of patients with dementia (n=156) were assessed with the Chilean version of FAB. Results: FAB showed good internal consistency (Cronbach's alpha=0.79) and acceptable validity based on the relationship with other variables. Factor analysis showed the unidimensionality of the instrument. Significant differences were found in the total FAB value between the HC and dementia groups. With the matched sample, the established cutoff point was 13.5, showing a sensitivity of 80.8% and a specificity of 90.4%. Regression analysis showed that education and age significantly predicted FAB performance in the healthy group. Finally, normative data are provided. Conclusions: This study shows that FAB is a useful tool to discriminate between healthy people and people with dementia. However, further studies are needed to explore the capacity of the instrument to characterize the dysexecutive syndrome in people with dementia in the Chilean population.


A Bateria de Avaliação Frontal (FAB) é um teste de rastreio que mede as funções executivas. Embora esse instrumento tenha sido validado em vários países, sua utilidade diagnóstica em uma população chilena ainda não foi estudada. Objetivos: (1) Adaptar a FAB para uma população chilena; (2) estudar as propriedades psicométricas da FAB em uma população chilena; (3) avaliar a influência sociodemográfica no desempenho da FAB em uma amostra de controles saudáveis; e (4) desenvolver dados normativos para este último grupo. Métodos: Um grupo controle saudável (n=344) e um grupo de pacientes com demência (n=156) foram avaliados com a versão chilena da FAB. Resultados: A FAB apresentou boa consistência interna (alfa de Cronbach=0,79) e validade aceitável com base na relação com outras variáveis. A análise fatorial mostrou a unidimensionalidade do instrumento. Diferenças significativas foram encontradas no valor total da FAB entre os grupos controle saudável e demência. Com a amostra pareada, o ponto de corte estabelecido foi de 13,5, que apresentou sensibilidade de 80,8% e especificidade de 90,4%. A análise de regressão mostrou que a escolaridade e a idade predisseram significativamente o desempenho da FAB no grupo saudável. Finalmente, os dados normativos são fornecidos. Conclusões: O presente estudo mostrou que a FAB é uma ferramenta útil para discriminar entre pessoas saudáveis e aquelas com demência. No entanto, mais estudos são necessários para explorar a capacidade do instrumento para caracterizar a síndrome disexecutiva em pessoas com demência na população chilena.

10.
IEEE Trans Cybern ; 51(2): 1070-1084, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31217140

RESUMO

Synergies have been adopted in prosthetic limb applications to reduce the complexity of design, but typically involve a single synergy setting for a population and ignore individual preference or adaptation capacity. However, personalization of the synergy setting is necessary for the effective operation of the prosthetic device. Two major challenges hinder the personalization of synergies in human-prosthesis interfaces (HPIs). The first is related to the process of human motor adaptation and the second to the variation in motor learning dynamics of individuals. In this paper, a systematic personalization of kinematic synergies for HPIs using online measurements from each individual is proposed. The task of reaching using the upper limb is described by an objective function and the interface is parameterized by a kinematic synergy. Consequently, personalizing the interface for a given individual can be formulated as finding an optimal personalized parameter. A structure to model the observed motor behavior that allows for the personalized traits of motor preference and motor learning is proposed, and subsequently used in an online optimization scheme to identify the synergies for an individual. The knowledge of the common features contained in the model enables online adaptation of the HPI to happen concurrently to human motor adaptation without the need to retune the personalization algorithm for each individual. Human-in-the-loop experimental results with able-bodied subjects, performed in a virtual reality environment to emulate amputation and prosthesis use, show that the proposed personalization algorithm was effective in obtaining optimal synergies with a fast uniform convergence speed across a group of individuals.


Assuntos
Membros Artificiais , Processamento de Sinais Assistido por Computador , Realidade Virtual , Adulto , Idoso , Algoritmos , Fenômenos Biomecânicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Desenho de Prótese , Interface Usuário-Computador , Adulto Jovem
11.
Annu Int Conf IEEE Eng Med Biol Soc ; 2021: 4615-4618, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34892242

RESUMO

In active prostheses, it is desired to achieve target poses for a given family of tasks, for example, in the task of forward reaching using a transhumeral prosthesis with coordinated joint movements. To do so, it is necessary to distinguish these target poses accurately using the input features (e.g. kinematic and sEMG) obtained from the human users. However, the input features have conventionally been selected through human observations and influenced heavily by the availability of sensors in this context, which may not always yield the most relevant information to differentiate the target poses in the given task. In order to better select from a pool of available input features, those most appropriate for a given set of target poses, a measure that correlates well with the resulting classification accuracy is required so that it can inform the interface design process. In this paper, a scatter-matrix based class separability measure is adopted to quantitatively evaluate the separability of the target poses from their corresponding input features. A human experiment was performed on ten able-bodied subjects. Subjects were asked to perform forward-reaching movements with their arms on nine target poses in a virtual reality (VR) platform and the corresponding kinematic information of their arm movement and muscle activities were recorded. The accuracy of the prosthetic interface in determining the intended target poses of the human user during forward reaching is evaluated for different combinations of input features, selected from the kinematic and sEMG sensors worn by the users. The results demonstrate that employing input features that yield a high separability measure between target poses results in a high accuracy in identifying the intended target poses in the execution of the task.


Assuntos
Membros Artificiais , Braço , Fenômenos Biomecânicos , Eletromiografia , Humanos , Movimento
12.
Conscious Cogn ; 19(1): 341-51, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20116292

RESUMO

This study focuses on Implicit learning (IL) in children. One of the main debates in this field concerns the occurrence of IL indicators in experimental settings and its manifestation in different populations. In this research, we are looking for evidence of the occurrence of IL in normal children and in children with Attention Deficit Hyperactive Disorder (ADHD), based on the relationship between accuracy, reaction time and event-related potentials (ERPs). Our results show differences between the analyzed groups with respect to markers for electrophysiological activity and reaction time, but not for accuracy. In consequence, we suggest that research in IL should explore different indicators and their relationship with the cognitive processing levels involved. In addition, IL might involve different forms of information processing in normal children and children with ADHD. We discuss the possible impact of these findings for future research.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Cognição/fisiologia , Potenciais Evocados/fisiologia , Aprendizagem/fisiologia , Tempo de Reação/fisiologia , Atenção/fisiologia , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Biomarcadores , Encéfalo/fisiopatologia , Criança , Comportamento de Escolha , Eletroencefalografia/estatística & dados numéricos , Feminino , Jogos Experimentais , Humanos , Masculino , Testes Neuropsicológicos , Estimulação Luminosa , Desempenho Psicomotor/fisiologia , Inconsciente Psicológico
13.
RSC Med Chem ; 11(8): 940-949, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-33479689

RESUMO

Unpublished data from our labs led us to hypothesize that activated protein C (aPC) may initiate an anti-inflammatory signal in endothelial cells by modulating both the integrin αVß3 and protease-activated receptor 2 (PAR2), which may exist in close proximity on the cellular surface. To test this hypothesis and to probe the possible inflammation-related pathway, we designed and synthesized dual-targeting ligands composed of modified versions of two αVß3 ligands and two agonists of PAR2. These novel ligands were connected via copper-catalyzed alkyne-azide cycloadditions with polyethylene glycol (PEG) spacers of variable length. Initial in vitro pharmacology with EA.hy926 and HUVEC endothelial cells indicated that these ligands are effective binders of αVß3 and potent agonists of PAR2. These were also used in preliminary studies investigating their effects on PAR2 signaling in the presence of inflammatory agents, and represent the first examples of ligands targeting both PARs and integrins, though concurrent binding to αVß3 and PAR2 has not yet been demonstrated.

14.
IEEE Trans Neural Syst Rehabil Eng ; 28(12): 2966-2977, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33151883

RESUMO

Synergistic prostheses enable the coordinated movement of the human-prosthetic arm, as required by activities of daily living. This is achieved by coupling the motion of the prosthesis to the human command, such as the residual limb movement in motion-based interfaces. Previous studies demonstrated that developing human-prosthetic synergies in joint-space must consider individual motor behaviour and the intended task to be performed, requiring personalisation and task calibration. In this work, an alternative synergy-based strategy, utilising a synergistic relationship expressed in task-space, is proposed. This task-space synergy has the potential to replace the need for personalisation and task calibration with a model-based approach requiring knowledge of the individual user's arm kinematics, the anticipated hand motion during the task and voluntary information from the prosthetic user. The proposed method is compared with surface electromyography-based and joint-space synergy-based prosthetic interfaces in a study of motor behaviour and task performance on able-bodied subjects using a VR-based transhumeral prosthesis. Experimental results showed that for a set of forward reaching tasks the proposed task-space synergy achieves comparable performance to joint-space synergies without the need to rely on time-consuming calibration processes or human motor learning. Case study results with an amputee subject motivate the further development of the proposed task-space synergy method.


Assuntos
Membros Artificiais , Atividades Cotidianas , Eletromiografia , Mãos , Humanos , Movimento
15.
Front Neurosci ; 14: 348, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32395102

RESUMO

The appropriate sensory information feedback is important for the success of an object grasping and manipulation task. In many scenarios, the need arises for multiple feedback information to be conveyed to a prosthetic hand user simultaneously. The multiple sets of information may either (1) directly contribute to the performance of the grasping or object manipulation task, such as the feedback of the grasping force, or (2) simply form additional independent set(s) of information. In this paper, the efficacy of simultaneously conveying two independent sets of sensor information (the grasp force and a secondary set of information) through a single channel of feedback stimulation (vibrotactile via bone conduction) to the human user in a prosthetic application is investigated. The performance of the grasping task is not dependent to the second set of information in this study. Subject performance in two tasks: regulating the grasp force and identifying the secondary information, were evaluated when provided with either one corresponding information or both sets of feedback information. Visual feedback is involved in the training stage. The proposed approach is validated on human-subject experiments using a vibrotactile transducer worn on the elbow bony landmark (to realize a non-invasive bone conduction interface) carried out in a virtual reality environment to perform a closed-loop object grasping task. The experimental results show that the performance of the human subjects on either task, whilst perceiving two sets of sensory information, is not inferior to that when receiving only one set of corresponding sensory information, demonstrating the potential of conveying a second set of information through a bone conduction interface in an upper limb prosthetic task.

16.
ACS Med Chem Lett ; 10(9): 1353-1356, 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31531209

RESUMO

The concept recently postulated by Stein and co-workers (Science 2017, 355, 966) that mu opioid receptor (MOR) agonists possessing amines with attenuated basicity show pH-dependent activity and can selectively act at damaged, low pH tissues has been additionally supported by in vitro studies reported here. We synthesized and tested analogs of fentanyl possessing one or two fluorine atoms at the beta position of the phenethylamine side chain, with additional fluorines optionally added to the benzene ring of the side chain. These compounds were synthesized in 1 to 3 steps from commercial building blocks. The novel bis-fluorinated analog RR-49 showed superior pH sensitivity, with full efficacy relative to DAMGO, but with 19-fold higher potency (IC50) in a MOR cAMP assay at pH 6.5 versus 7.4. Such compounds hold significant promise as analgesics for inflammatory pain with reduced abuse potential.

17.
Front Psychol ; 10: 2024, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31551874

RESUMO

This study aimed to test the impact of play on the development of executive functions (EFs) in preschoolers. Thirty-two games were designed to be collectively played in groups by 70 children, in their regular classes. The games were specifically designed to promote the development of the three components of EFs: inhibition (behavioral or cognitive), working memory, and cognitive flexibility. The games focused on each function were of three types: playground games, expression games, and classroom games. Sixty 45 min play sessions were held on consecutive days for 3 months, always in the first period. The sessions were guided by two members of the research team, assisted by the four teachers of the participating classes. The intervention was carried out in two highly socially vulnerable schools in the city of Santiago de Chile. Four classes were studied in total: two experimental groups and two controls. The classes were selected using a questionnaire on teacher-student interaction quality and an age homogeneity criterion. EFs were evaluated using the Hearts and Flowers task at three points: before the intervention (T1), immediately after the end of the intervention (T2), and 8 months after the end of the intervention (T3). The results show a significant difference in the growth of EFs by comparing the experimental and control groups (p = 0.04) between T1 and T3. They also reveal a strong correlation between EFs measures at T1 and mathematics performance at T3. These results are discussed within the context of the guidelines proposed by Diamond and Ling (2016) and Barnett (2011) regarding what an EFs promotion program needs to be considered effective and high quality. The program presented in this study meets most of the requisites mentioned by the authors, which proves that following these guidelines guarantees a high probability of success.

18.
ACS Med Chem Lett ; 10(1): 121-126, 2019 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-30655958

RESUMO

A novel class of bivalent ligands targeting putative protease-activated receptor (PAR) heteromers has been prepared based upon reported antagonists for the subtypes PAR1 and PAR2. Modified versions of the PAR1 antagonist RWJ-58259 containing alkyne adapters were connected via cycloaddition reactions to azide-capped polyethylene glycol (PEG) spacers attached to imidazopyridazine-based PAR2 antagonists. Initial studies of the PAR1-PAR2 antagonists indicated that they inhibited G alpha q-mediated calcium mobilization in endothelial and cancer cells driven by both PAR1 and PAR2 agonists. Compounds of this novel class hold promise for the prevention of restenosis, cancer cell metastasis, and other proliferative disorders.

19.
Annu Int Conf IEEE Eng Med Biol Soc ; 2018: 3194-3197, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30441072

RESUMO

Current prosthesis command interfaces only allow for a single degree of freedom to be commanded at a time, making coordinated motion difficult to achieve. Thus it becomes crucial to develop methods that complement these interfaces to allow for intuitive coordinated arm motion. Kinematic synergies have been shown as an alternate method where the motion of the prosthetic device is coordinated with that of the residual limb. In this paper, the mapping between the parameters of a kinematic synergy model and a measure of task performance is established experimentally in order to test the applicability of online optimization methods for the identification of synergies. To achieve this, a cost function that captures the objective of the reaching task and a linear kinematic synergy model were chosen. A human experiment was developed in a Virtual Reality (VR) platform in order to determine the synergy-performance relationship. The experiments were performed on 10 able-bodied subjects. The relationship observed between the synergy parameter and the reaching task cost function suggests existing online optimization methods may be applicable.


Assuntos
Membros Artificiais , Extremidade Superior , Fenômenos Biomecânicos , Humanos , Análise e Desempenho de Tarefas
20.
Rev Neurol ; 57(3): 103-11, 2013 Aug 01.
Artigo em Espanhol | MEDLINE | ID: mdl-23881614

RESUMO

INTRODUCTION: Children with neurological diseases that impose severe limitations on their mobility have a deficient quality of life (QL). AIMS: To study whether the QL of such patients improves with the application of a programme of audiovisual stimulation. PATIENTS AND METHODS: A prospective study was conducted on nine children, six of whom were males (mean age: 42.6 ± 28.6 months), with severely limited mobility and who had been hospitalised for long periods. Two audiovisual stimulation programmes were produced and applied, together with videos, by means of a specially designed structure. The stimulus was applied twice a day for 10 minutes over 20 days. The first ten days the stimulus was carried out in a passive manner and the second block of ten days it was performed with the guidance of the observer. Biological, behavioural and cognitive variables were recorded and an adapted QL survey was applied. RESULTS: Three cases of spinal muscular atrophy, two of congenital muscular dystrophy, two of myopathy and two with other conditions were diagnosed. Eight patients completed the follow-up. From the baseline point of view, they presented a regular QL (7.2 ± 1.7 points; median: 7.0; range: 6-10), which improved to good on finishing the therapy (9.4 ± 1.2 points; median: 9.0; range: 8-11), with an intra-individual difference of 2.1 ± 1.6 (median: 2.5; range: -1 to 4; CI 95% = 0.83-3.42; p = 0.006). Improved cognition and a favourable perception in the caregivers were detected. No changes took place in the biological or behavioural variables. CONCLUSIONS: Audiovisual stimulation can be used to enhance the quality of life of children with severely limited mobility.


TITLE: Estimulacion audiovisual en niños con limitacion grave de la motricidad: mejora su calidad de vida?Introduccion. Los niños con enfermedades neurologicas que condicionan una limitacion grave de la movilidad tienen una calidad de vida (CV) deficiente. Objetivo. Estudiar si la CV de dichos pacientes mejora con la aplicacion de un programa de estimulacion audiovisual. Pacientes y metodos. Estudio prospectivo en nueve niños, seis de ellos varones (edad media: 42,6 ± 28,6 meses), con limitacion grave de la movilidad, hospitalizados de manera prolongada. Se elaboraron dos programas de estimulo audiovisual que, junto con videos, se aplicaron mediante una estructura especialmente diseñada. La frecuencia fue de dos veces al dia, por 10 minutos, durante 20 dias. Los primeros diez dias se llevo a cabo de manera pasiva y los segundos diez con guia del observador. Se registraron variables biologicas, conductuales, cognitivas y se aplico una encuesta de CV adaptada. Resultados. Se diagnosticaron tres casos de atrofia muscular espinal, dos de distrofia muscular congenita, dos de miopatia y dos con otros diagnosticos. Ocho pacientes completaron el seguimiento. Desde el punto de vista basal, presentaron CV regular (7,2 ± 1,7 puntos; mediana: 7,0; rango: 6-10), que mejoraba a buena al finalizar (9,4 ± 1,2 puntos; mediana: 9,0; rango: 8-11), con diferencia intraindividual de 2,1 ± 1,6 (mediana: 2,5; rango: ­1 a 4; IC 95% = 0,83-3,42; p = 0,006). Se detecto mejoria en cognicion y percepcion favorable de los cuidadores. No hubo cambio en las variables biologicas ni conductuales. Conclusion. Mediante la estimulacion audiovisual es posible mejorar la calidad de vida de niños con limitacion grave de la movilidad.


Assuntos
Estimulação Acústica , Recursos Audiovisuais , Criança Hospitalizada/psicologia , Transtornos dos Movimentos/terapia , Estimulação Luminosa , Criança , Comportamento Infantil , Pré-Escolar , Chile , Cognição , Emoções , Feminino , Humanos , Lactente , Masculino , Atividade Motora , Transtornos dos Movimentos/psicologia , Distrofias Musculares/congênito , Distrofias Musculares/psicologia , Distrofias Musculares/terapia , Percepção , Estudos Prospectivos , Qualidade de Vida , Atrofias Musculares Espinais da Infância/psicologia , Atrofias Musculares Espinais da Infância/terapia
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