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1.
Sci Data ; 11(1): 555, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38816429

ABSTRACT

Intracranial aneurysms (IAs) are present in 2-6% of the global population and can be catastrophic upon rupture with a mortality rate of 30-50%. IAs are commonly detected through time-of-flight magnetic resonance angiography (TOF-MRA), however, this data is rarely available for research and training purposes. The provision of imaging resources such as TOF-MRA images is imperative to develop new strategies for IA detection, rupture prediction, and surgical training. To support efforts in addressing data availability bottlenecks, we provide an open-access TOF-MRA dataset comprising 63 patients, of which 24 underwent interval surveillance imaging by TOF-MRA. Patient scans were evaluated by a neuroradiologist, providing aneurysm and vessel segmentations, clinical annotations, 3D models, in addition to 3D Slicer software environments containing all this data for each patient. This dataset is the first to provide interval surveillance imaging for supporting the understanding of IA growth and stability. This dataset will support computational and experimental research into IA dynamics and assist surgical and radiology training in IA treatment.


Subject(s)
Intracranial Aneurysm , Magnetic Resonance Angiography , Intracranial Aneurysm/diagnostic imaging , Humans
2.
J Autism Dev Disord ; 2024 Feb 23.
Article in English | MEDLINE | ID: mdl-38393438

ABSTRACT

Rehabilitative and habilitative therapies can help children with disabilities increase independence and overall wellbeing. However, children and their caregivers face many barriers to accessing these therapies and often rely on the school for therapy access. Given the limited resources available within the special education system, increasing parent involvement in special education therapies could improve service delivery. However, providers must first understand what parents need to participate in therapies before attempting to engage families. 217 parents completed an online survey consisting of the Parent-Therapist Partnership Survey and demographic questionnaires about theirfamiliesand their child[ren] with disabilities. The percentage of needs parents endorsed as important and thepercentageofimportantneedsendorsedasunmetwere calculated. Differences across demographic variables were assessed. Overall, parents reported an average of 75% of needs as important with significantly more needs endorsed as important regarding being an informed, engaged member of the child's care team (M = 83%) than needs related to support and guidance (M = 65%, p < 0.001). Furthermore, parentsreportedan average of 58% of important needs as unmet, with no significant differences in subscale averages. Significant associations were found for race/ethnicity, education, income, partner availability, number of children with disabilities in the household, transportation access, neighborhood opportunities, parent efficacy and social, emotional, and behavioral concerns. Parents reported a high percentage of needs as important, but a large percentage of these important needs were considered unmet. Significant disparities based on racial/ethnic identities and access to resources were found. In order to successfully engage parents in special education therapy activities, providers must work to understand and address parents' engagement needs, paying special attention to each family's unique circumstances to optimize engagement.

3.
Disabil Health J ; 17(1): 101537, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37805314

ABSTRACT

BACKGROUND: Children and youth with special health care needs (CYSHCN) are at an increased risk for abuse and neglect, and they experience worse outcomes during and after child protective services involvement, as compared to typically developing peers. Identifying and monitoring these vulnerable youth is essential for reducing disparities and optimizing service delivery. However, many states, including Illinois, lack systems for efficient identification and monitoring. OBJECTIVE: (1) To examine existing Illinois Department of Children and Family Services (ILDCFS) data systems to determine if a source exists that would allow for identification and monitoring of CYSHCN; and (2) To understand ILDCFS personnel's experience with identifying and monitoring CYSHCN. METHODS: First, relevant ILDCFS data sources were identified, pulled, and examined for completeness. Second, ILDCFS personnel completed a mixed-methods survey assessing how they identified and monitored CYSHCN as well as what barriers they experienced in conducting these activities. Conceptual content analysis was utilized to obtain counts of different methods used to track and monitor youth as well as to identify barriers to these processes. RESULTS: Six data sources were identified as being relevant through ILDCFS' data systems, but none were complete enough for effectively tracking and identifying CYSHCN. Survey responses indicated no standardized, systemic process for identifying and monitoring CYSHCN, with many personnel relying on reports from other involved parties. CONCLUSIONS: In order to identify CYSHCN and monitor well-being, a standardized process within ILDCFS systems is needed to provide complete, accurate, and timely data for CYSHCN, allowing for both system-wide and individual-level monitoring.


Subject(s)
Child Health Services , Disabled Children , Child , Humans , Adolescent , Illinois , Child Welfare , Health Services Needs and Demand , Information Systems
4.
Nature ; 619(7971): 724-732, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37438522

ABSTRACT

The presence and distribution of preserved organic matter on the surface of Mars can provide key information about the Martian carbon cycle and the potential of the planet to host life throughout its history. Several types of organic molecules have been previously detected in Martian meteorites1 and at Gale crater, Mars2-4. Evaluating the diversity and detectability of organic matter elsewhere on Mars is important for understanding the extent and diversity of Martian surface processes and the potential availability of carbon sources1,5,6. Here we report the detection of Raman and fluorescence spectra consistent with several species of aromatic organic molecules in the Máaz and Séítah formations within the Crater Floor sequences of Jezero crater, Mars. We report specific fluorescence-mineral associations consistent with many classes of organic molecules occurring in different spatial patterns within these compositionally distinct formations, potentially indicating different fates of carbon across environments. Our findings suggest there may be a diversity of aromatic molecules prevalent on the Martian surface, and these materials persist despite exposure to surface conditions. These potential organic molecules are largely found within minerals linked to aqueous processes, indicating that these processes may have had a key role in organic synthesis, transport or preservation.

5.
J Community Psychol ; 51(6): 2430-2441, 2023 Jul.
Article in English | MEDLINE | ID: mdl-35695353

ABSTRACT

This study identifies challenges and advantages parents faced in navigating therapy service delivery for their child with disabilities during the COVID-19 pandemic. As part of an online survey, 171 parents of children with disabilities answered four, free response questions regarding the therapy services their children received during the pandemic. A grounded theory approach was used to identify top challenges, barriers, advantages, and recommendations. Challenges included children's poor response to telehealth services, lack of parent training, and technological challenges. Advantages included fewer barriers to service access and increased family involvement. Parents largely recommended shorter, more frequent teletherapy sessions, and resuming in-person services. To improve parent engagement in, and the sustainability of, services, parent feedback should inform service delivery design and implementation. Incorporating parent feedback about service delivery can decrease disparities in access and increase parent engagement in child services both generally, and during periods of service disruption.


Subject(s)
COVID-19 , Disabled Children , Child , Humans , Pandemics , Parents
6.
Fam Syst Health ; 41(1): 92-100, 2023 03.
Article in English | MEDLINE | ID: mdl-35708922

ABSTRACT

INTRODUCTION: The novel coronavirus disease 2019 (COVID-19) significantly disrupted therapy service delivery for children with disabilities and their families. Parents of children with disabilities have been particularly impacted as a large degree of responsibility has been placed on them to both manage and deliver therapies remotely. However, little is known regarding whether sociodemographic factors are associated with parents' perceptions of therapy service delivery during COVID-19. This study explored the relationship between sociodemographic factors and parents' satisfaction with therapies for children with disabilities during COVID-19. METHOD: Two hundred seven parents of children with disabilities completed an online survey battery that included the Family-Provider Partnership Scale and sociodemographic characteristics and assessed their satisfaction with their child[ren]'s therapies during COVID-19. RESULTS: Access to telehealth, receipt of only school-based therapies, parent education, number of household essential workers, and total number of children were associated with satisfaction with therapy service and/or the family-provider partnership. DISCUSSION: By better understanding the association between sociodemographic factors and parent perception of therapy service delivery, providers can better support families in optimizing service delivery during the remainder of COVID-19 mitigation efforts and during future periods of service disruption. This study provides insight into the sociodemographic characteristics that are associated with lower levels of satisfaction and thus require more tailored support from providers. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Subject(s)
COVID-19 , Disabled Children , Child , Humans , Parents , Surveys and Questionnaires , Family Characteristics
7.
Redox Biol ; 59: 102550, 2023 02.
Article in English | MEDLINE | ID: mdl-36470129

ABSTRACT

Neuronal oxidative stress has been implicated in aging and neurodegenerative disease. Here we investigated the impact of elevated oxidative stress induced in mouse spinal cord by deletion of Mn-Superoxide dismutase (MnSOD) using a neuron specific Cre recombinase in Sod2 floxed mice (i-mn-Sod2 KO). Sod2 deletion in spinal cord neurons was associated with mitochondrial alterations and peroxide generation. Phenotypically, i-mn-Sod2 KO mice experienced hindlimb paralysis and clasping behavior associated with extensive demyelination and reduced nerve conduction velocity, axonal degeneration, enhanced blood brain barrier permeability, elevated inflammatory cytokines, microglia activation, infiltration of neutrophils and necroptosis in spinal cord. In contrast, spinal cord motor neuron number, innervation of neuromuscular junctions, muscle mass, and contractile function were not altered. Overall, our findings show that loss of MnSOD in spinal cord promotes a phenotype of demyelination, inflammation and progressive paralysis that mimics phenotypes associated with progressive multiple sclerosis.


Subject(s)
Multiple Sclerosis , Neurodegenerative Diseases , Mice , Animals , Mitochondria , Superoxide Dismutase/genetics , Motor Neurons , Superoxide Dismutase-1/genetics , Phenotype , Paralysis/genetics , Inflammation/genetics
8.
J Autism Dev Disord ; 2022 Nov 03.
Article in English | MEDLINE | ID: mdl-36329299

ABSTRACT

Parents of children with disabilities are an important part of their child's special education team. However, parents often have limited involvement in school-based therapies that are provided as part of a child's Individualized Education Program. The field lacks tools to assess the domain and extent of parent needs for optimal engagement in their child's special education therapies. Study one assessed the Parent-Therapist Partnership Survey's (PTPS) (formerly known as the Needs of Parents Questionnaire -School-Based Therapy Version) measure's clarity, fit, and comprehensiveness. Study two assessed the factor structure and internal consistency. Two factors emerged - Need to Be an Informed, Engaged Member of Their Child's Team, and Need for Support and Guidance. Internal consistency was 0.93 for the overall scale. The PTPS can serve as a powerful measure to better identify opportunities to engage parents in school therapeutic goals while improving parent-provider collaboration in school-based therapies.

9.
J Neurosci ; 42(31): 5992-6006, 2022 08 03.
Article in English | MEDLINE | ID: mdl-35760531

ABSTRACT

Cognitive decline is a debilitating aspect of aging and neurodegenerative diseases such as Alzheimer's disease are closely associated with mitochondrial dysfunction, increased reactive oxygen species, neuroinflammation, and astrogliosis. This study investigated the effects of decreased mitochondrial antioxidant response specifically in astrocytes on cognitive performance and neuronal function in C57BL/6J mice using a tamoxifen-inducible astrocyte-specific knockout of manganese superoxide dismutase (aSOD2-KO), a mitochondrial matrix antioxidant that detoxifies superoxide generated during mitochondrial respiration. We reduced astrocyte SOD2 levels in male and female mice at 11-12 months of age and tested in an automated home cage (PhenoTyper) apparatus for diurnal patterns, spatial learning, and memory function at 15 months of age. aSOD2-KO impaired hippocampal-dependent spatial working memory and decreased cognitive flexibility in the reversal phase of the testing paradigm in males. Female aSOD2-KO showed no learning and memory deficits compared with age-matched controls despite significant reduction in hippocampal SOD2 expression. aSOD2-KO males further showed decreased hippocampal long-term potentiation, but paired-pulse facilitation was unaffected. Levels of d-serine, an NMDA receptor coagonist, were also reduced in aSOD2-KO mice, but female knockouts showed a compensatory increase in serine racemase expression. Furthermore, aSOD2-KO mice demonstrated increased density of astrocytes, indicative of astrogliosis, in the hippocampus compared with age-matched controls. These data demonstrate that reduction in mitochondrial antioxidant stress response in astrocytes recapitulates age-related deficits in cognitive function, d-serine availability, and astrogliosis. Therefore, improving astrocyte mitochondrial homeostasis may provide a therapeutic target for intervention for cognitive impairment in aging.SIGNIFICANCE STATEMENT Diminished antioxidant response is associated with increased astrogliosis in aging and in Alzheimer's disease. Manganese superoxide dismutase (SOD2) is an antioxidant in the mitochondrial matrix that detoxifies superoxide and maintains mitochondrial homeostasis. We show that astrocytic ablation of SOD2 impairs hippocampal-dependent plasticity in spatial working memory, reduces long-term potentiation of hippocampal neurons and levels of the neuromodulator d-serine, and increases astrogliosis, consistent with defects in advanced aging and Alzheimer's disease. Our data provide strong evidence for sex-specific effects of astrocytic SOD2 functions in age-related cognitive dysfunction.


Subject(s)
Alzheimer Disease , Astrocytes , Superoxide Dismutase , Alzheimer Disease/metabolism , Animals , Antioxidants/metabolism , Astrocytes/metabolism , Cognition/physiology , Female , Gliosis/metabolism , Hippocampus/metabolism , Male , Memory, Short-Term , Mice , Mice, Inbred C57BL , Serine/metabolism , Sex Factors , Superoxide Dismutase/genetics , Superoxides/metabolism
10.
Res Dev Disabil ; 123: 104183, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35134739

ABSTRACT

BACKGROUND: Parent engagement in therapeutic services for children with disabilities could optimize service delivery while addressing service disparities. However, service providers must first understand parents' needs to effectively involve parents. AIMS: This study examines what needs parents identify as important when engaging with school-based therapies and how well these needs are being met. METHODS AND PROCEDURES: Parents of children with Individualized Education Plans rated statements related to their needs for trust, information, support and guidance, and personal needs when engaging with their child's therapies. Parents also provided demographic information on them and their child[ren] with a disability. OUTCOMES AND RESULTS: Parents endorsed an average of 83 % of needs as important but 51 % of needs as unmet. On average, 65 % of needs related to feeling trusted by service providers were met. In contrast, needs related to receivings upport and guidance (M = 58 %), information (M = 55 %), and addressing parent's own needs (M = 53 %) were frequently unmet. Parents indicated that needs related to feeling trusted by service providers were most frequently met. In contrast, needs related to receiving information were most frequently unmet. Race/ethnicity and number of children with a disability influenced the number of needs endorsed as important and unmet. CONCLUSION: This feasibility study suggests that parents find a variety of needs regarding their interactions with school-based providers as important to them. However, given the high proportion of needs indicated being unmet, significant gaps likely exist in effectively engaging parents, especially for Parents of Color and parents with multiple children with disabilities. IMPLICATIONS: This study provides a list of tangible needs school-based providers can use to improve parent engagement with school-based therapies. School-based providers and administrators can use the needs identified as important and unmet in this study to create actionable steps that aim to improve parent engagement in school-based services.


Subject(s)
Disabled Children , Child , Humans , Parents , School Health Services , Schools
11.
Environ Res ; 207: 112142, 2022 05 01.
Article in English | MEDLINE | ID: mdl-34597660

ABSTRACT

Airborne microplastics (MPs) could have negative impacts on human health and pollute water, soil, and sediment. This study explored the distributions, compositions, and morphology of airborne microplastics in the indoor and ambient air in New Jersey, United States. Microplastic fibers, films, and fragments of Polystyrene (PS), Polyethylene terephthalate (PET), Polyethyelene (PE), Polyvinyl chloride (PVC) and Polypropylene (PP) were identified in office, hallway, classroom, and single-family house in this study. The deposition rates of synthetic fibers with length from 35 µm to 1000 µm were highest in the single-family house ((1.96 ± 1.09) × 104 fibers/m2/day) and lowest in the classroom ((6.20 ± 0.57) × 103 fibers/m2/day), suggesting that residential houses are a major source of microplastic fibers. However, for film-like plastics with surface areas ranging from 200 µm2 to 5000 µm2, a high deposition rate of (8.13 ± 2.17) × 103 films/m2/day was observed in the classroom, whereas the lowest deposition rate of (4.45 ± 0.27) × 103 films/m2/day was found in the hallway, probably because plastic films such as PE are intensively used in the classroom environments. The deposition rate of microplastics in the ambient air acquired on a building roof was only about 2-8% of the indoor deposition rates. The microplastics with similar textures but different sizes were identified in both total atmospheric deposition and particulate samples (PM2.5 and PM10), suggesting degradation from microplastics to nanoplastics. The main microplastics found in indoor air samples were PE fragments or fibers, different from those in the outdoor ambient air that were dominated by PVC fragments. These results unravel the properties of airborne microplastics in urban environments that are important to understanding their fate, transport, and potential health risks.


Subject(s)
Air Pollution, Indoor , Water Pollutants, Chemical , Air Pollution, Indoor/analysis , Environmental Monitoring/methods , Humans , Microplastics , New Jersey , Plastics , Water Pollutants, Chemical/analysis
12.
MMWR Morb Mortal Wkly Rep ; 70(45): 1575-1578, 2021 Nov 12.
Article in English | MEDLINE | ID: mdl-34758010

ABSTRACT

Influenza causes considerable morbidity and mortality in the United States. Between 2010 and 2020, an estimated 9-41 million cases resulted in 140,000-710,000 hospitalizations and 12,000-52,000 deaths annually (1). As the United States enters the 2021-22 influenza season, the potential impact of influenza illnesses is of concern given that influenza season will again coincide with the ongoing COVID-19 pandemic, which could further strain overburdened health care systems. The Advisory Committee on Immunization Practices (ACIP) recommends routine annual influenza vaccination for the 2021-22 influenza season for all persons aged ≥6 months who have no contraindications (2). To assess the potential impact of the COVID-19 pandemic on influenza vaccination coverage, the percentage change between administration of at least 1 dose of influenza vaccine during September-December 2020 was compared with the average administered in the corresponding periods in 2018 and 2019. The data analyzed were reported from 11 U.S. jurisdictions with high-performing state immunization information systems.* Overall, influenza vaccine administration was 9.0% higher in 2020 compared with the average in 2018 and 2019, combined. However, in 2020, the number of influenza vaccine doses administered to children aged 6-23 months and children aged 2-4 years, was 13.9% and 11.9% lower, respectively than the average for each age group in 2018 and 2019. Strategic efforts are needed to ensure high influenza vaccination coverage among all age groups, especially children aged 6 months-4 years who are not yet eligible to receive a COVID-19 vaccine. Administration of influenza vaccine and a COVID-19 vaccine among eligible populations is especially important to reduce the potential strain that influenza and COVID-19 cases could place on health care systems already overburdened by COVID-19.


Subject(s)
COVID-19/epidemiology , Influenza Vaccines/administration & dosage , Pandemics , Vaccination/statistics & numerical data , Adolescent , Adult , Advisory Committees , Aged , Centers for Disease Control and Prevention, U.S. , Child , Child, Preschool , Humans , Immunization/standards , Infant , Influenza, Human/epidemiology , Influenza, Human/prevention & control , Middle Aged , Seasons , United States/epidemiology , Young Adult
13.
J Raman Spectrosc ; 52(6): 1155-1166, 2021 Jun.
Article in English | MEDLINE | ID: mdl-34163097

ABSTRACT

Carbonate rocks record the oldest forms of life on Earth, and their geologic reconstruction requires multiple methods to determine physical and chemical processes before conclusions of ancient biosignatures are made. Since crystal orientation within rock fabric may be used to infer geologic settings, we present here a complementary Raman method to study the orientation of calcite (CaCO3) and dolomite [CaMg (CO3)2] minerals. The relative peak intensity ratio of the carbonate lattice Eg modes T and L reveals the crystallographic orientation of calcite and dolomite with respect to the incident light polarization. Our results for calcite show that when the incident laser light propagates down the crystallographic a/b axis: (1) the L mode is always greater in intensity than the T mode (I T < I L), and (2) the spectra are most intense at 45° and least intense at 90° polarization angles measured from around the c axis. Our results for dolomite show that (1) I T > I L when the incident light propagation is down the crystallographic c axis and (2) I T < I L when the incident light propagation is down the crystallographic a/b axis. This study reveals mineral orientation variation related to deposition and paragenesis within limestone and dolostone samples. The method presented yields information related to growth and deformation during diagenetic and metamorphic alteration and may be used in research seeking to identify the fabric parameters of any calcite or dolomite containing rock. The compositional and structural data obtained from Raman mapping is useful in structural geology, materials science, and biosignature research.

14.
J Pediatr ; 231: 168-177.e1, 2021 04.
Article in English | MEDLINE | ID: mdl-33359629

ABSTRACT

OBJECTIVE: To assess the impact of the novel coronavirus disease 2019 (COVID-19) pandemic on the delivery of, and parent satisfaction with, therapy services for children with disabilities in early intervention, school, and outpatient settings. STUDY DESIGN: There were 207 parents of children with disabilities who completed a web-based survey about their child[ren]'s access to, and satisfaction with, therapy services during COVID-19. Parents also completed the Family-Provider Partnership Scale and the Telehealth Satisfaction Scale. Satisfaction was compared between families receiving therapies in school, early intervention, outpatient, and multiple settings. RESULTS: Forty-four percent of parents reported low satisfaction with their child[ren]'s therapy services during the pandemic. Access to telehealth positively predicted overall satisfaction and satisfaction with the family-provider partnership, whereas receiving school-based therapies negatively predicted overall satisfaction and satisfaction with the family-provider partnership. CONCLUSIONS: School-based therapies are legally mandated for eligible students, free of cost to families, integrated in the academic setting, and less burdensome on parents than other services. Thus, given the disparity in parental satisfaction regarding school-based service delivery, addressing therapy delivery in school-based settings during the duration of COVID-19 is critical for preventing increased disparities and more effectively meeting children's needs. Telehealth seems to be a promising option for continuing high-quality services during the duration of the COVID-19 pandemic and for families who face barriers in accessing services in general. Future studies are warranted with larger and more diverse samples, as well as longitudinal studies that monitor service access and parent satisfaction throughout the remainder of the pandemic.


Subject(s)
COVID-19/epidemiology , Child Health Services/organization & administration , Disabled Children , Health Services Accessibility/organization & administration , School Health Services/organization & administration , Telemedicine/organization & administration , Adolescent , Adult , Aged , Child , Child, Preschool , Hospitalization , Humans , Infant , Infant, Newborn , Middle Aged , Parents/psychology , Patient Satisfaction , Young Adult
15.
J Exp Child Psychol ; 202: 104981, 2021 02.
Article in English | MEDLINE | ID: mdl-33161340

ABSTRACT

Two experiments examined factors that predicted children's tendencies to match objects versus relations across scenes when no instruction was given. Specifically, we assessed the presence of higher relational responding in children by (a) age, (b) greater presumed experience in generating relations through socialization in China versus the United States, and (c) in children with greater manipulated experience via a relational priming task. Experiment 1 showed that Chinese and U.S. children across all ages showed an initial bias to match objects versus relations across scenes. However, older children in both regions were more likely to notice features of the task that indicated attending to relational matches was a more reliable solution, and shifted their responding toward relations over the course of the task. Experiment 2 replicated the object-mapping bias and age effects within U.S. children while also examining the impact of directly manipulating children's relational experiences to test the malleability of the bias. Before the main scene-mapping task, children did a relation generation task known to prime attention to relations. This did not override the initial bias toward object mapping, but it magnified the role of age, making older children increasingly sensitive to task features that prompted relational matches, further shifting their responding toward relations over the course of the task.


Subject(s)
Attentional Bias , Child , Child, Preschool , China , Female , Humans , Male , United States
16.
Acta Biomater ; 104: 1-16, 2020 03 01.
Article in English | MEDLINE | ID: mdl-31945506

ABSTRACT

Retinal degenerative disorders, such as age-related macular degeneration (AMD), are one of the leading causes of blindness worldwide, however, treatments to completely stop the progression of these debilitating conditions are non-existent. Researchers require sophisticated models that can accurately represent the native structure of human retinal tissue to study these disorders. Current in vitro models used to study the retina are limited in their ability to fully recapitulate the structure and function of the retina, Bruch's membrane and the underlying choroid. Recent developments in the field of induced pluripotent stem cell technology has demonstrated the capability of retinal pigment epithelial cells to recapitulate AMD-like pathology. However, such studies utilise unsophisticated, bio-inert membranes to act as Bruch's membrane and support iPSC-derived retinal cells. This review presents a concise summary of the properties and function of the Bruch's membrane-retinal pigment epithelium complex, the initial pathogenic site of AMD as well as the current status for materials and fabrication approaches used to generate in vitro models of this complex tissue. Finally, this review explores required advances in the field of in vitro retinal modelling. STATEMENT OF SIGNIFICANCE: Retinal degenerative disorders such as age-related macular degeneration are worldwide leading causes of blindness. Previous attempts to model the Bruch's membrane-retinal pigment epithelial complex, the initial pathogenic site of age-related macular degeneration, have lacked the sophistication to elucidate valuable insights into disease mechanisms. Here we provide a detailed account of the morphological, physical and chemical properties of Bruch's membrane which may aid the fabrication of more sophisticated and physiologically accurate in vitro models of the retina, as well as various fabrication techniques to recreate this structure. This review also further highlights some recent advances in some additional challenging aspects of retinal tissue modelling including integrated fluid flow and photoreceptor alignment.


Subject(s)
Biomimetics , Bruch Membrane/cytology , Cell Communication , Models, Biological , Retina/cytology , Biomechanical Phenomena , Humans
17.
Dev Psychobiol ; 62(7): 895-908, 2020 11.
Article in English | MEDLINE | ID: mdl-31531855

ABSTRACT

Although much is known about the influences of early life experiences on the neurobiology and behavior of macaque models of child development, there is scant literature on cognitive development with respect to early rearing. Here, we examined the effects of rearing condition on affective reactivity and cognitive development in infant rhesus macaques. Infants were pseudo-randomly assigned to one of the two rearing conditions: nursery reared (NR, N = 32; 16 peer-reared, 16 surrogate-peer-reared) or mother-peer-reared (MPR, N = 7). During the first month of life, infants were administered the Primate Neonatal Neurobehavioral Assessment (PNNA). Beginning at 4 months old, infants were tested on cognitive tasks that assessed reward association, cognitive flexibility, and impulsivity. We found no gross cognitive differences between MPR and NR infants. However, MPR infants were more reactive than NR infants on the PNNA. Additionally, reactivity on the PNNA correlated with impulsivity, such that infants who were more reactive at 1 month of age completed fewer trials correctly on this task at 8-10 months. These findings are the first to directly compare cognitive development in MPR and NR infants, and add to the existing literature elucidating the influences of early social experience on temperament and development.


Subject(s)
Cognition , Macaca mulatta/psychology , Social Environment , Animals , Animals, Newborn/growth & development , Animals, Newborn/psychology , Female , Macaca mulatta/growth & development , Male , Neuropsychological Tests
18.
Acta Biomater ; 101: 102-116, 2020 01 01.
Article in English | MEDLINE | ID: mdl-31610339

ABSTRACT

This study investigates the utility of a tailored poly(ethylene glycol) diacrylate-crosslinked porous polymeric tissue engineering scaffold, with mechanical properties specifically optimised to be comparable to that of mammalian brain tissue for 3D human neural cell culture. Results obtained here demonstrate the attachment, proliferation and terminal differentiation of both human induced pluripotent stem cell- and embryonic stem cell-derived neural precursor cells (hPSC-NPCs) throughout the interconnected porous network within laminin-coated scaffolds. Phenotypic data and functional analyses are presented demonstrating that this material supports terminal in vitro neural differentiation of hPSC-NPCs to a mixed population of viable neuronal and glial cells for periods of up to 49 days. This is evidenced by the upregulation of TUBB3, MAP2, SYP and GFAP gene expression, as well as the presence of the proteins ßIII-TUBULIN, NEUN, MAP2 and GFAP. Functional maturity of neural cells following 49 days 3D differentiation culture was tested via measurement of intracellular calcium. These analyses revealed spontaneously active, synchronous and rhythmic calcium flux, as well as response to the neurotransmitter glutamate. This tailored construct has potential application as an improved in vitro human neurogenesis model with utility in platform drug discovery programs. STATEMENT OF SIGNIFICANCE: The interconnected porosity of polyHIPE scaffolds exhibits the ability to support three-dimensional neural cell network formation due to limited resistance to cellular migration and re-organisation. The previously developed scaffold material displays mechanical properties similar to that of the mammalian brain. This research also employs the utility of pluripotent stem cell-derived neural cells which are of greater clinical relevance than primary neural cell lines. This scaffold material has future potential in better mimicking three-dimensional neural networks found in the human brain and may result in improved in vitro models for disease modelling and drug screening applications.


Subject(s)
Antigens, Differentiation/biosynthesis , Cell Differentiation , Gene Expression Regulation , Induced Pluripotent Stem Cells/metabolism , Neural Stem Cells/metabolism , Tissue Scaffolds/chemistry , Humans , Induced Pluripotent Stem Cells/cytology , Neural Stem Cells/cytology , Porosity
19.
Sci Transl Med ; 11(523)2019 12 18.
Article in English | MEDLINE | ID: mdl-31852797

ABSTRACT

Zika virus (ZIKV) infection of pregnant women is associated with congenital Zika syndrome (CZS) and no vaccine is available, although several are being tested in clinical trials. We tested the efficacy of ZIKV DNA vaccine VRC5283 in a rhesus macaque model of congenital ZIKV infection. Most animal vaccine experiments have a set pathogen exposure several weeks or months after vaccination. In the real world, people encounter pathogens years or decades after vaccination, or may be repeatedly exposed if the virus is endemic. To more accurately mimic how this vaccine would be used, we immunized macaques before conception and then exposed them repeatedly to ZIKV during early and mid-gestation. In comparison to unimmunized animals, vaccinated animals had a significant reduction in peak magnitude and duration of maternal viremia, early fetal loss, fetal infection, and placental and fetal brain pathology. Vaccine-induced neutralizing antibody titers on the day of first ZIKV exposure were negatively associated with the magnitude of maternal viremia, and the absence of prolonged viremia was associated with better fetal outcomes. These data support further clinical development of ZIKV vaccine strategies to protect against negative fetal outcomes.


Subject(s)
Vaccination/methods , Vaccines, DNA/therapeutic use , Zika Virus Infection/prevention & control , Animals , Antibodies, Neutralizing/metabolism , Female , Macaca mulatta , Pregnancy , Pregnancy Complications, Infectious/immunology , Pregnancy Complications, Infectious/prevention & control , Viremia/immunology , Viremia/prevention & control , Zika Virus/immunology , Zika Virus/pathogenicity
20.
Am J Primatol ; 81(9): e23037, 2019 09.
Article in English | MEDLINE | ID: mdl-31515850

ABSTRACT

The importance of marmosets for comparative and translational science has grown in recent years because of their relatively rapid development, birth cohorts of twins, family social structure, and genetic tractability. Despite this, they remain understudied in investigations of affective processes. In this methodological note, we establish the validity of using noninvasive commercially available equipment to record cardiac physiology and compute indices of autonomic nervous system activity-a major component of affective processes. Specifically, we recorded electrocardiogram and impedance cardiogram, from which we derived heart rate, respiration rate, measures of high-frequency heart rate variability (indices of parasympathetic autonomic nervous system activity), and ventricular contractility (an index of sympathetic autonomic nervous system activity). Our methods produced physiologically plausible data, and further, animals with increased heart rates during testing were also more reactive to isolation from their social partner and presentation of novel objects, though no relationship was observed between reactivity and specific indices of parasympathetic or sympathetic nervous system activity.


Subject(s)
Autonomic Nervous System/physiology , Callithrix/physiology , Cardiography, Impedance/methods , Electrocardiography/methods , Heart/physiology , Psychophysiology/methods , Animals , Callithrix/psychology , Heart Rate/physiology , Male , Respiratory Rate/physiology
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