RESUMEN
OBJECTIVE: Physical activity in people with stroke remains low despite considerable research. This overview aimed to provide high-level synthesis and aid clinical decision-making. The Capability, Opportunity, Motivation-Behaviour (COM-B) model was used to classify interventions to understand which components improve physical activity behaviour in people with stroke. DATA SOURCES: CINAHL, Cochrane Database, MEDLINE, PEDro, PsychINFO, SPORTDiscus. REVIEW METHODS: A systematic search was conducted (November 2023) to identify reviews of interventions to improve physical activity in people with stroke. Results were screened and assessed for eligibility. Participant characteristics, intervention classification using COM-B, and effect of intervention were extracted. Quality was assessed using AMSTAR2, and Corrected Cover Analysis for study overlap. Narrative synthesis was used to understand components of interventions to improve physical activity behaviour. RESULTS: 1801 references were screened and 29 full-text references assessed for eligibility. Twenty reviews were included. Quality ranged from critically low (n = 3) to high (n = 10). Study overlap calculated using corrected cover area indicated slight overlap (0.028) and minimal reporting bias.The majority of participants were mobile with mild stroke and community dwelling. Twenty-three interventions were classified using COM-B. Three of twelve interventions classified to one aspect of the COM-B were effective. Fourteen of sixteen effective interventions combined at least two COM-B elements, ten of these combined capability and motivation. CONCLUSION: Interventions including at least two elements of the COM-B are most likely to improve physical activity in mobile stroke survivors. Further research is needed to understand physical activity behaviour in those with moderate to severe stroke.
Asunto(s)
Ejercicio Físico , Motivación , Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Humanos , Rehabilitación de Accidente Cerebrovascular/métodos , Conductas Relacionadas con la SaludRESUMEN
OBJECTIVE: Topical tretinoin is the mainstay of treatment for photoageing, despite the risk of skin irritation. Cosmetic combination anti-ageing formulations may offer similar efficacy to tretinoin, while improving on tolerability. We aim to demonstrate facial appearance benefits of a novel triple-active cosmetic formulation containing 4-hexylresorcinol, retinyl propionate, and niacinamide and to identify transcriptomic biomarkers underpinning these benefits. METHODS: A cosmetic prototype formulation containing 4-hexylresorcinol, retinyl propionate, and niacinamide was evaluated ex vivo and in a clinical study. For ex vivo experiments, the cosmetic formulation was applied for 3 days to healthy surgical discard skin from female donors aged 31-51 years, with tissues harvested for gene expression and histologic analyses. In the clinical study, females aged 47-66 years with moderate-to-severe overall visual photodamage on the face applied either topical 0.02% tretinoin or the cosmetic formulation to the face for 16 weeks and to forearms for 1 week, with forearm biopsies taken for gene expression analyses. Visual grading for facial photodamage and VISIA-CR images was taken throughout the clinical study. Safety was visually assessed during site visits, and adverse event monitoring was conducted throughout. RESULTS: Gene expression analyses in both studies revealed modulation of pathways associated with skin rejuvenation, with several genes of interest identified due to being implicated in ageing and differentially expressed following the application of the cosmetic formulation. Reversal of a consensus skin ageing gene signature was observed with the cosmetic formulation and tretinoin in the ex vivo and clinical studies. Both the cosmetic formulation and tretinoin clinically improved the overall appearance of photoageing, crow's feet, lines, wrinkles, and pores. Adverse event reporting showed that the cosmetic formulation caused less skin irritation than tretinoin. CONCLUSION: In a double-blind clinical study, the novel triple-active cosmetic combination formulation improved the visual appearance of photoageing similarly to prescription tretinoin. The cosmetic formulation and tretinoin reversed a consensus gene signature associated with ageing. Together with adverse event reporting, these results suggest that the cosmetic formulation may be a well-tolerated and efficacious alternative to tretinoin for improving the visual features of photoageing.
OBJECTIF: Le trétinoine topique est le pilier du traitement du photovieillissement, malgré le risque d'irritation cutanée. Les formulations cosmétiques combinés antiâge peuvent offrir une efficacité similaire à la trétinoine, tout en améliorant la tolérance. Notre objectif est de démontrer les avantages esthétiques pour l'apparence du visage d'une nouvelle formulation cosmétique triple active contenant du 4hexylrésorcinol, du rétinyl propionate et de la niacinamide, et d'identifier les biomarqueurs transcriptomiques sousjacents à ces avantages. MÉTHODES: Une formulation cosmétique prototype contenant du 4hexylrésorcinol, du rétinyl propionate et de la niacinamide a été évaluée ex vivo et lors d'une étude clinique. Pour les expériences ex vivo, la formulation cosmétique a été appliquée pendant 3 jours sur des peaux saines issues de donatrices âgées de 31 à 51 ans, avec prélèvement de tissus pour l'analyse de l'expression génique et l'histologie. Dans l'étude clinique, des femmes âgées de 47 à 66 ans présentant un photovieillissement visuel global modéré a sévère sur le visage ont appliqué soit du trétinoine topique à 0.02%, soit la formulation cosmétique sur le visage pendant 16 semaines et sur les avantbras pendant 1 semaine, avec des biopsies d'avantbras prélevées pour l'analyse de l'expression génique. L'évaluation visuelle du photovieillissement facial et les images VISIACR ont été réalisées tout au long de l'étude clinique. La sécurité a été évaluée visuellement lors des visites sur site, et une surveillance des événements indésirables a été effectuée. RÉSULTATS: Les analyses de l'expression génique dans les deux études ont révélé une modulation des voies associées au rajeunissement cutané, avec plusieurs gènes d'intérêts identifiés en raison de leur implication dans le vieillissement et de leur expression différentielle suite à l'application de la formulation cosmétique. Une inversion de la signature génique du vieillissement cutané consensuelle a été observée avec la formulation cosmétique et la trétinoine dans les études ex vivo et cliniques. La formulation cosmétique et la trétinoine ont toutes deux amélioré cliniquement l'apparence globale du photovieillissement, des pattes d'oie, des ridules, des rides et des pores. Les rapports sur les événements indésirables ont montré que la formulation cosmétique provoquait moins d'irritation cutanée que la trétinoine. CONCLUSION: Dans une étude clinique en double aveugle, la nouvelle formulation cosmétique triple active a amélioré l'apparence visuelle du photovieillissement de manière similaire à la trétinoine sur ordonnance. La formulation cosmétique et la trétinoine ont inversé une signature génique consensuelle associée au vieillissement. En tenant compte des rapports sur les événements indésirables, ces résultats suggèrent que la formulation cosmétique pourrait constituer une alternative bien tolérée et efficace à la trétinoine pour améliorer les caractéristiques visuelles du photovieillissement.
RESUMEN
High-quality communicative interactions between caregivers and children provide a foundation for children's social and cognitive skills. Although most studies examining these types of interactions focus on child language outcomes, this paper takes another tack. It examines whether communicative, dyadic interactions might also relate to child executive function (EF) skills and whether child language might mediate this relation. Using a subset of data from the NICHD Study of Early Child Care and Youth Development, dyadic interactions between 2-year-olds and their mothers were coded for three behaviors: symbol-infused joint engagement, routines and rituals, and fluency and connectedness. Child language was assessed at age 3 and three facets of EF (self-regulation, sustained attention, and verbal working memory) were assessed at age 4.5. Structural equation modeling showed that dyadic interaction related to later child sustained attention and verbal working memory, indirectly through child language and directly related with child self-regulation. This suggests that communicative interactions with caregivers that include both verbal and non-verbal elements relate to child EF, in part through child language. Our findings have implications for the role of caregiver interactions in the development of language and cognitive skills more broadly. RESEARCH HIGHLIGHTS: Using structural equation modeling, we examined how communicative interactions between caregivers and toddlers relate to preschool executive function skills Communicative interactions relate to later language which in turn relates to sustained attention and verbal working memory in preschool Communicative interactions relate directly to self-regulation in preschool Associations between communicative interactions, language, and executive function vary across facets of executive function and may not be unidirectional.
Asunto(s)
Función Ejecutiva , Lenguaje , Femenino , Humanos , Preescolar , Adolescente , Función Ejecutiva/fisiología , Comunicación , Madres/psicología , Memoria a Corto PlazoRESUMEN
Brain enlargement has been observed in children with autism spectrum disorder (ASD), but the timing of this phenomenon, and the relationship between ASD and the appearance of behavioural symptoms, are unknown. Retrospective head circumference and longitudinal brain volume studies of two-year olds followed up at four years of age have provided evidence that increased brain volume may emerge early in development. Studies of infants at high familial risk of autism can provide insight into the early development of autism and have shown that characteristic social deficits in ASD emerge during the latter part of the first and in the second year of life. These observations suggest that prospective brain-imaging studies of infants at high familial risk of ASD might identify early postnatal changes in brain volume that occur before an ASD diagnosis. In this prospective neuroimaging study of 106 infants at high familial risk of ASD and 42 low-risk infants, we show that hyperexpansion of the cortical surface area between 6 and 12 months of age precedes brain volume overgrowth observed between 12 and 24 months in 15 high-risk infants who were diagnosed with autism at 24 months. Brain volume overgrowth was linked to the emergence and severity of autistic social deficits. A deep-learning algorithm that primarily uses surface area information from magnetic resonance imaging of the brain of 6-12-month-old individuals predicted the diagnosis of autism in individual high-risk children at 24 months (with a positive predictive value of 81% and a sensitivity of 88%). These findings demonstrate that early brain changes occur during the period in which autistic behaviours are first emerging.
Asunto(s)
Trastorno del Espectro Autista/diagnóstico , Trastorno del Espectro Autista/patología , Encéfalo/crecimiento & desarrollo , Encéfalo/patología , Trastorno del Espectro Autista/genética , Trastorno del Espectro Autista/psicología , Preescolar , Salud de la Familia , Femenino , Humanos , Lactante , Estudios Longitudinales , Masculino , Neuroimagen , Pronóstico , Riesgo , Conducta SocialRESUMEN
Infant vocalizations are early-emerging communicative markers shown to be atypical in autism spectrum disorder (ASD), but few longitudinal, prospective studies exist. In this study, 23,850 infant vocalizations from infants at low (LR)- and high (HR)-risk for ASD (HR-ASD = 23, female = 3; HR-Neg = 35, female = 13; LR = 32, female = 10; 80% White; collected from 2007 to 2017 near Philadelphia) were analyzed at 6, 12, and 24 months. At 12 months, HR-ASD infants produced fewer vocalizations than HR-Neg infants. From 6 to 24 months, HR-Neg infants demonstrated steeper vocalization growth compared to HR-ASD and LR infants. Finally, among HR infants, vocalizing at 12 months was associated with language, social phenotype, and diagnosis at age 2. Infant vocalizing is an objective behavioral marker that could facilitate earlier detection of ASD.
Asunto(s)
Trastorno del Espectro Autista , Trastorno Autístico , Trastorno del Espectro Autista/diagnóstico , Biomarcadores , Comunicación , Femenino , Humanos , Lactante , Fenotipo , Estudios Prospectivos , HermanosRESUMEN
Infants from low-socioeconomic status (SES) households hear a projected 30 million fewer words than their higher-SES peers. In a recent study, Hirsh-Pasek et al. (Psychological Science, 2015; 26: 1071) found that in a low-income sample, fluency and connectedness in exchanges between caregivers and toddlers predicted child language a year later over and above quantity of talk (Hirsh-Pasek et al., Psychological Science, 2015; 26: 1071). Here, we expand upon this study by examining fluency and connectedness in two higher-SES samples. Using data from the NICHD Study of Early Child Care and Youth Development, we sampled 20 toddlers who had low, average, and high language outcomes at 36 months from each of 2 groups based on income-to-needs ratio (INR; middle and high) and applied new coding to the mother-toddler interaction at 24 months. In the high-INR group, the quality of mother-toddler interaction at 24 months accounted for more variability in language outcomes a year later than did quantity of talk, quality of talk, or sensitive parenting. These results could not be accounted for by child language ability at 24 months. These effects were not found in the middle-INR sample. Our findings suggest that when the quality of interaction, fluency and connectedness, predicts language outcomes, it is a robust relation, but it may not be universal.
Asunto(s)
Desarrollo del Lenguaje , Lenguaje , Relaciones Madre-Hijo , Responsabilidad Parental , Clase Social , Preescolar , Femenino , Humanos , Renta , Estudios Longitudinales , MasculinoRESUMEN
Variants in RORB have been reported in eight individuals with epilepsy, with phenotypes ranging from eyelid myoclonia with absence epilepsy to developmental and epileptic encephalopathies. We identified novel RORB variants in 11 affected individuals from four families. One was from whole genome sequencing and three were from RORB screening of three epilepsy cohorts: developmental and epileptic encephalopathies (n = 1021), overlap of generalized and occipital epilepsy (n = 84), and photosensitivity (n = 123). Following interviews and review of medical records, individuals' seizure and epilepsy syndromes were classified. Three novel missense variants and one exon 3 deletion were predicted to be pathogenic by in silico tools, not found in population databases, and located in key evolutionary conserved domains. Median age at seizure onset was 3.5 years (0.5-10 years). Generalized, predominantly absence and myoclonic, and occipital seizures were seen in all families, often within the same individual (6/11). All individuals with epilepsy were photosensitive, and seven of 11 had cognitive abnormalities. Electroencephalograms showed generalized spike and wave and/or polyspike and wave. Here we show a striking RORB phenotype of overlap of photosensitive generalized and occipital epilepsy in both individuals and families. This is the first report of a gene associated with this overlap of epilepsy syndromes.
Asunto(s)
Epilepsias Parciales/genética , Epilepsia Generalizada/genética , Epilepsia Refleja/genética , Predisposición Genética a la Enfermedad/genética , Miembro 2 del Grupo F de la Subfamilia 1 de Receptores Nucleares/genética , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Mutación , LinajeRESUMEN
Infant gross motor development is vital to adaptive function and predictive of both cognitive outcomes and neurodevelopmental disorders. However, little is known about neural systems underlying the emergence of walking and general gross motor abilities. Using resting state fcMRI, we identified functional brain networks associated with walking and gross motor scores in a mixed cross-sectional and longitudinal cohort of infants at high and low risk for autism spectrum disorder, who represent a dimensionally distributed range of motor function. At age 12 months, functional connectivity of motor and default mode networks was correlated with walking, whereas dorsal attention and posterior cingulo-opercular networks were implicated at age 24 months. Analyses of general gross motor function also revealed involvement of motor and default mode networks at 12 and 24 months, with dorsal attention, cingulo-opercular, frontoparietal, and subcortical networks additionally implicated at 24 months. These findings suggest that changes in network-level brain-behavior relationships underlie the emergence and consolidation of walking and gross motor abilities in the toddler period. This initial description of network substrates of early gross motor development may inform hypotheses regarding neural systems contributing to typical and atypical motor outcomes, as well as neurodevelopmental disorders associated with motor dysfunction.
Asunto(s)
Encéfalo/diagnóstico por imagen , Encéfalo/crecimiento & desarrollo , Desarrollo Infantil/fisiología , Red Nerviosa/diagnóstico por imagen , Red Nerviosa/crecimiento & desarrollo , Caminata/fisiología , Trastorno del Espectro Autista/diagnóstico por imagen , Trastorno del Espectro Autista/fisiopatología , Preescolar , Femenino , Humanos , Lactante , Estudios Longitudinales , Imagen por Resonancia Magnética/tendencias , Masculino , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/crecimiento & desarrolloRESUMEN
Initiating joint attention (IJA), the behavioral instigation of coordinated focus of 2 people on an object, emerges over the first 2 years of life and supports social-communicative functioning related to the healthy development of aspects of language, empathy, and theory of mind. Deficits in IJA provide strong early indicators for autism spectrum disorder, and therapies targeting joint attention have shown tremendous promise. However, the brain systems underlying IJA in early childhood are poorly understood, due in part to significant methodological challenges in imaging localized brain function that supports social behaviors during the first 2 years of life. Herein, we show that the functional organization of the brain is intimately related to the emergence of IJA using functional connectivity magnetic resonance imaging and dimensional behavioral assessments in a large semilongitudinal cohort of infants and toddlers. In particular, though functional connections spanning the brain are involved in IJA, the strongest brain-behavior associations cluster within connections between a small subset of functional brain networks; namely between the visual network and dorsal attention network and between the visual network and posterior cingulate aspects of the default mode network. These observations mark the earliest known description of how functional brain systems underlie a burgeoning fundamental social behavior, may help improve the design of targeted therapies for neurodevelopmental disorders, and, more generally, elucidate physiological mechanisms essential to healthy social behavior development.
Asunto(s)
Atención/fisiología , Encéfalo/crecimiento & desarrollo , Encéfalo/fisiología , Encéfalo/diagnóstico por imagen , Mapeo Encefálico , Desarrollo Infantil/fisiología , Preescolar , Femenino , Humanos , Lactante , Imagen por Resonancia Magnética , Masculino , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/crecimiento & desarrollo , Vías Nerviosas/fisiología , Pruebas Neuropsicológicas , Psicología InfantilRESUMEN
Children's early language environments are related to later development. Little is known about this association in siblings of children with autism spectrum disorder (ASD), who often experience language delays or have ASD. Fifty-nine 9-month-old infants at high or low familial risk for ASD contributed full-day in-home language recordings. High-risk infants produced more vocalizations than low-risk peers; conversational turns and adult words did not differ by group. Vocalization differences were driven by a subgroup of "hypervocal" infants. Despite more vocalizations overall, these infants engaged in less social babbling during a standardized clinic assessment, and they experienced fewer conversational turns relative to their rate of vocalizations. Two ways in which these individual and environmental differences may relate to subsequent development are discussed.
Asunto(s)
Trastorno del Espectro Autista/fisiopatología , Desarrollo Infantil/fisiología , Conducta del Lactante/fisiología , Hermanos , Conducta Social , Conducta Verbal/fisiología , Femenino , Humanos , Lactante , Masculino , Riesgo , Procesamiento de Señales Asistido por ComputadorRESUMEN
The association between developmental trajectories of language-related white matter fiber pathways from 6 to 24 months of age and individual differences in language production at 24 months of age was investigated. The splenium of the corpus callosum, a fiber pathway projecting through the posterior hub of the default mode network to occipital visual areas, was examined as well as pathways implicated in language function in the mature brain, including the arcuate fasciculi, uncinate fasciculi, and inferior longitudinal fasciculi. The hypothesis that the development of neural circuitry supporting domain-general orienting skills would relate to later language performance was tested in a large sample of typically developing infants. The present study included 77 infants with diffusion weighted MRI scans at 6, 12 and 24 months and language assessment at 24 months. The rate of change in splenium development varied significantly as a function of language production, such that children with greater change in fractional anisotropy (FA) from 6 to 24 months produced more words at 24 months. Contrary to findings from older children and adults, significant associations between language production and FA in the arcuate, uncinate, or left inferior longitudinal fasciculi were not observed. The current study highlights the importance of tracing brain development trajectories from infancy to fully elucidate emerging brain-behavior associations while also emphasizing the role of the splenium as a key node in the structural network that supports the acquisition of spoken language.
Asunto(s)
Desarrollo del Lenguaje , Lenguaje , Vías Nerviosas/fisiología , Inteligibilidad del Habla/fisiología , Desarrollo Infantil , Cuerpo Calloso , Imagen de Difusión por Resonancia Magnética , Humanos , Lactante , Fibras Nerviosas MielínicasRESUMEN
Mutations in COL4A1 are well described and result in brain abnormalities manifesting with severe neurological deficits including cerebral palsy, intellectual disability, and focal epilepsy. Families with mutations in COL4A2 are now emerging with a similar phenotype. We describe a family with an autosomal dominant disorder comprising porencephaly, focal epilepsy, and lens opacities, which was negative for mutations in COL4A1. Using whole exome sequencing of three affected individuals from three generations, we identified a rare variant in COL4A2. This COL4A2 (c.2399G>A, p.G800E, CCDS41907.1) variant was predicted to be damaging by multiple bioinformatics tools and affects an invariable glycine residue that is essential for the formation of collagen IV heterotrimers. The cataracts identified in this family expand the phenotypic spectrum associated with mutations in COL4A2 and highlight the increasing overlap with phenotypes associated with COL4A1 mutations.
Asunto(s)
Catarata/diagnóstico , Catarata/genética , Colágeno Tipo IV/genética , Genes Dominantes , Mutación , Porencefalia/diagnóstico , Porencefalia/genética , Adolescente , Adulto , Anciano , Encéfalo/patología , Exoma , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Imagen por Resonancia Magnética , Masculino , LinajeRESUMEN
BACKGROUND: Recent evidence suggests that restricted and repetitive behaviors may differentiate children who develop autism spectrum disorder (ASD) by late infancy. How these core symptoms manifest early in life, particularly among infants at high risk for the disorder, is not well characterized. METHODS: Prospective, longitudinal parent-report data (Repetitive Behavior Scales-Revised) were collected for 190 high-risk toddlers and 60 low-risk controls from 12 to 24 months of age. Forty-one high-risk children were classified with ASD at age 2. Profiles of repetitive behavior were compared between groups using generalized estimating equations. RESULTS: Longitudinal profiles for children diagnosed with ASD differed significantly from high- and low-risk children without the disorder on all measures of repetitive behavior. High-risk toddlers without ASD were intermediate to low risk and ASD positive counterparts. Toddlers with ASD showed significantly higher rates of repetitive behavior across subtypes at the 12-month time point. Repetitive behaviors were significantly correlated with adaptive behavior and socialization scores among children with ASD at 24 months of age, but were largely unrelated to measures of general cognitive ability. CONCLUSIONS: These findings suggest that as early as 12 months of age, a broad range of repetitive behaviors are highly elevated in children who go on to develop ASD. While some degree of repetitive behavior is elemental to typical early development, the extent of these behaviors among children who develop ASD appears highly atypical.
Asunto(s)
Trastorno Autístico/psicología , Conducta Estereotipada , Factores de Edad , Estudios de Casos y Controles , Desarrollo Infantil , Preescolar , Estudios Transversales , Femenino , Humanos , Lactante , Estudios Longitudinales , MasculinoRESUMEN
Gestures are an important social communication skill that infants and toddlers use to convey their thoughts, ideas, and intentions. Research suggests that early gesture use has important downstream impacts on developmental processes, such as language learning. However, autistic children are more likely to have challenges in their gestural development. The current study expands upon previous literature on the differences in gesture use between young autistic and non-autistic toddlers by collecting data using a parent-report questionnaire called the MCDI-Words and Gestures at three time points, 12, 18, and 24 months of age. Results (N = 467) showed that high-likelihood infants who later met diagnostic criteria for ASD (n = 73 HL-ASD) have attenuated gesture growth from 12 to 24 months for both deictic gestures and symbolic gestures when compared to high-likelihood infants who later did not meet criteria for ASD (n = 249 HL-Neg) and low-likelihood infants who did not meet criteria for ASD (n = 145 LL-Neg). Other social communicative skills, like play behaviors and imitation, were also found to be impacted in young autistic children when compared to their non-autistic peers. Understanding early differences in social communication growth before a formal autism diagnosis can provide important insights for early intervention.
Asunto(s)
Trastorno del Espectro Autista , Trastorno Autístico , Lactante , Humanos , Trastorno Autístico/diagnóstico , Gestos , Trastorno del Espectro Autista/diagnóstico , Desarrollo del LenguajeRESUMEN
Diffusion MR imaging has received increasing attention in the neuroimaging community, as it yields new insights into the microstructural organization of white matter that are not available with conventional MRI techniques. While the technology has enormous potential, diffusion MRI suffers from a unique and complex set of image quality problems, limiting the sensitivity of studies and reducing the accuracy of findings. Furthermore, the acquisition time for diffusion MRI is longer than conventional MRI due to the need for multiple acquisitions to obtain directionally encoded Diffusion Weighted Images (DWI). This leads to increased motion artifacts, reduced signal-to-noise ratio (SNR), and increased proneness to a wide variety of artifacts, including eddy-current and motion artifacts, "venetian blind" artifacts, as well as slice-wise and gradient-wise inconsistencies. Such artifacts mandate stringent Quality Control (QC) schemes in the processing of diffusion MRI data. Most existing QC procedures are conducted in the DWI domain and/or on a voxel level, but our own experiments show that these methods often do not fully detect and eliminate certain types of artifacts, often only visible when investigating groups of DWI's or a derived diffusion model, such as the most-employed diffusion tensor imaging (DTI). Here, we propose a novel regional QC measure in the DTI domain that employs the entropy of the regional distribution of the principal directions (PD). The PD entropy quantifies the scattering and spread of the principal diffusion directions and is invariant to the patient's position in the scanner. High entropy value indicates that the PDs are distributed relatively uniformly, while low entropy value indicates the presence of clusters in the PD distribution. The novel QC measure is intended to complement the existing set of QC procedures by detecting and correcting residual artifacts. Such residual artifacts cause directional bias in the measured PD and here called dominant direction artifacts. Experiments show that our automatic method can reliably detect and potentially correct such artifacts, especially the ones caused by the vibrations of the scanner table during the scan. The results further indicate the usefulness of this method for general quality assessment in DTI studies.
Asunto(s)
Artefactos , Encéfalo/patología , Imagen de Difusión por Resonancia Magnética/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Imagen de Difusión por Resonancia Magnética/normas , Entropía , Humanos , Procesamiento de Imagen Asistido por Computador/normas , Control de CalidadRESUMEN
Elucidating the neural basis of joint attention in infancy promises to yield important insights into the development of language and social cognition, and directly informs developmental models of autism. We describe a new method for evaluating responding to joint attention performance in infancy that highlights the 9- to 10-month period as a time interval of maximal individual differences. We then demonstrate that fractional anisotropy in the right uncinate fasciculus, a white matter fiber bundle connecting the amygdala to the ventral-medial prefrontal cortex and anterior temporal pole, measured in 6-month-olds predicts individual differences in responding to joint attention at 9 months of age. The white matter microstructure of the right uncinate was not related to receptive language ability at 9 months. These findings suggest that the development of core nonverbal social communication skills in infancy is largely supported by preceding developments within right lateralized frontotemporal brain systems.
Asunto(s)
Atención , Trastorno Autístico/fisiopatología , Lóbulo Frontal/patología , Amígdala del Cerebelo/patología , Anisotropía , Conducta , Encéfalo/patología , Mapeo Encefálico/métodos , Imagen de Difusión por Resonancia Magnética/métodos , Composición Familiar , Femenino , Humanos , Individualidad , Lactante , Aprendizaje , Masculino , Fibras Nerviosas Mielínicas/patología , Vías Nerviosas , Factores de TiempoRESUMEN
Heart transplantation (HTP) is a life-saving therapy for selected individuals with end-stage refractory heart failure. Despite improvements in quality of life and survival, HTP recipients' peak aerobic power (peak VO2) remains up to 50% lower than age-matched healthy control subjects owing to abnormal cardiovascular and skeletal muscle function. Currently, little is known regarding the effect of exercise training (ET) to improve peak VO2 after HTP. This brief review aims to summarise existing evidence regarding the role of ET on peak VO2 and its determinants, highlights the upper limits of endurance performance in highly trained HTP athletes, and identifies areas for future HTP exercise rehabilitation research.
Asunto(s)
Trasplante de Corazón , Calidad de Vida , Humanos , Ejercicio Físico/fisiología , Terapia por Ejercicio , Músculo Esquelético , Consumo de OxígenoRESUMEN
Chimeric antigen receptor (CAR)-T cell therapy is efficacious against many haematological malignancies, but challenges remain when using this cellular immunotherapy for treating solid tumours. Classical 2D in vitro models fail to recapitulate the complexity of the tumour microenvironment, whilst in vivo models, such as patient-derived xenografts, are costly and labour intensive. Microfluidic technologies can provide miniaturized solutions to assess CAR-T therapies in 3D complex preclinical models of solid tumours. Here, we present a novel microfluidic immunoassay for the evaluation of CAR-T cell cytotoxicity and targeting specificity on 3D spheroids containing cancer cells and stromal cells. Monitoring the interaction between CAR-T cells and spheroid co-cultures, we show that CAR-T cells home towards target-expressing cancer cells and elicit a cytotoxic effect. Testing CAR-T cells in combination therapies, we show that CAR-T cell cytotoxicity is enhanced with anti-PD-L1 therapy and carboplatin chemotherapy. We propose this proof-of-concept microfluidic immunoassay as a material-saving, pre-clinical screening tool for quantification of cell therapy efficacy.
RESUMEN
We present a new method for the surface capture of proteins in cell-free protein synthesis (CFPS). We demonstrate the spontaneous self-assembly of the protein BslA into functionalizable surfaces on the surface of a CFPS reaction chamber. We show that proteins can be covalently captured by such surfaces, using "Catcher/Tag" technology. Importantly, proteins of interest can be captured either when synthesised in situ by CFPS above the BslA surfaces, or when added as pure protein. The simplicity and cost efficiency of this method suggest that it will find many applications in cell-free-based methods.