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1.
Australas J Dermatol ; 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38764392

RESUMO

Kava induced dermatitis has been reported in previous case series, however the histology has rarely been described. This case report details an erythematous eruption associated with Kava ingestion and the associated folliculocentric sebaceous inflammation found on histological analysis.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38335943

RESUMO

OBJECTIVE: Cement volumes are increasingly linked to orthopedic oncology and neurosurgical outcomes (construct durability, adjacent fracture), but manual cement volumetry remains time prohibitive. The authors aim to report performance of PACS-integrated volumetric software specifically for barium-enhanced polymethylmethacrylate cement. METHODS: Institutional review board-approved single-institution retrospective review of patients from 2019-2022 undergoing kyphoplasty for pathological compression fractures with a quantitative cement infuser providing true cement volume. An operator blinded to true cement volumes retrospectively performed software-assisted volumetry on follow-up computed tomography scans. RESULTS: Included were 91 kyphoplasty levels in 56 patients: mean age, 62 years (range, 34-85 years), 73% female. True cement volume (available for 44 of 66 procedures) was mean 4.5 mL per level (range, 1.2-15.6 mL). Measured cement volume (available for all procedures) yielded a mean of 6.1 mL per level (range, 1.5-27.9 mL). For the 57 levels (39 patients) where both true and measured cement volumes were available, linear regression intercept and slope were 1.46 (95% CI = 0.97-1.95, P < 0.001) and 0.52 (CI = 0.47-0.57, P < 0.001), respectively, suggesting measured volume averaged 1.46 mL greater than true volume, with each additional milliliter of measured volume corresponding to approximately 0.52 mL of true volume. There was no significant difference in the relationship between estimated and actual cement volume in thoracic levels (intercept = -0.24, CI = -1.13 to 0.66, P = 0.61; slope = 0.03, CI = -0.14 to 0.19, P = 0.73) compared with lumbar levels. The goodness-of-fit of the regression model was strong (R2 = 0.81). Discrepancies ranged from 90% underestimation to 52% overestimation; average, 17% overestimation. CONCLUSIONS: Semi-automated volumetry maintained a strong correlation with true volumes across the thoracic and lumbar curvatures, overestimating cement volume by a mean of 17% or 1.46 mL.

3.
Radiol Artif Intell ; 6(2): e230147, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38381039

RESUMO

See also the commentary by Sitek in this issue. Supplemental material is available for this article.


Assuntos
Pneumonia , Criança , Humanos , Zâmbia , Pulmão , Tórax
4.
J Chem Phys ; 158(6): 064301, 2023 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-36792525

RESUMO

An alternative approach to density functional theory based on self-consistent field theory for ring polymers is applied to neutral atoms hydrogen to neon in their ground-states. The spontaneous emergence of an atomic shell structure and spherical symmetry-breaking of the total electron density are predicted by the model using the ideas of polymer excluded-volume between pairs of electrons to enforce the Pauli-exclusion principle and an exact electron self-interaction correction. The Pauli potential is approximated by neglecting inter-atomic correlations along with other types of correlations, and comparisons to Hartree-Fock theory are made, which also ignores correlations. The model shows excellent agreement with Hartree-Fock theory to within the standards of orbital-free density functional theory for the atomic binding energies and density profiles of the first six elements, providing exact matches for the elements hydrogen and helium. The predicted shell structure starts to deviate significantly past the element neon, and spherical symmetry-breaking is first predicted to occur at carbon instead of boron. The self-consistent field theory energy functional that describes the model is decomposed into thermodynamic components to trace the origin of spherical symmetry-breaking. It is found to arise from the electron density approaching closer to the nucleus in non-spherical distributions, which lowers the energy despite resulting in frustration between the quantum kinetic energy, electron-electron interaction, and the Pauli exclusion interaction. The symmetry-breaking effect is found to have a minimal impact on the binding energies, which suggests that the spherical-averaging approximation used in previous work is physically reasonable when investigating atomic systems. The pair density contour plots display behavior similar to polymer macro-phase separation, where individual electron pairs occupy single lobe structures that together form a dumbbell shape analogous to the 2p orbital shape. It is further shown that the predicted densities satisfy known constraints and produce the same total electronic density profile that is predicted by other formulations of quantum mechanics.

5.
J Phys Chem A ; 126(2): 325-332, 2022 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-34994568

RESUMO

A density functional theory based on polymer self-consistent field theory is applied to systems of two atoms in order to show that this approach is capable of predicted molecular bonding. Periodic table elements from hydrogen up to neon are examined and homonuclear diatomic molecules are found to form for H2, N2, O2, and F2, in agreement with known results. The heteronuclear molecules CO and HF, which are known to exist under ambient conditions, are also found to be stable. Bond lengths for most of these molecules agree with experimental results to within less than 8%, with the exception of O2 and F2 which deviate more significantly. The bonding energy for H2 is given and is within 16% of the known value, but fundamental vibrational frequencies do not agree well with experiment. The main approximations of the theory are very simple and include a Fermi-Amaldi correction to the electron-electron interaction to account for self-interactions and a basic expression for the Pauli potential to account for the exclusion principle. The self-consistent equations are solved in terms of basis functions that encode the cylindrical symmetry of diatomic molecules. Since orbitals are not used, the approach is related to orbital-free density functional theory.

6.
Drugs Context ; 102021.
Artigo em Inglês | MEDLINE | ID: mdl-33828606

RESUMO

This narrative review addresses scabies, a highly contagious, pruritic infestation of the skin caused by the mite Sarcoptes scabiei var hominis. Scabies is a common disorder that has a prevalence worldwide estimated to be between 200 and 300 million cases per year. Infestation is of greatest concern in children, the elderly, immunocompromised people and resource-poor endemic populations at risk of chronic complications. A diagnosis of scabies involves a clinical suspicion, a detailed targeted history, clinical examination and contact tracing. Dermoscopy and microscopy, where available, is confirmatory. Due to its infectivity and transmissibility, the management for scabies requires a multimodal approach: topical antiscabetic agents are the first line for most cases of childhood classic scabies and their contacts, which must also be identified and treated to prevent treatment failure and reacquisition. Environmental strategies to control fomite-related reinfestation are also recommended. Oral ivermectin, where available, is reserved for use in high-risk cases in children or in mass drug administration programmes in endemic communities. The prevention of downstream complications of scabies includes surveillance, early identification and prompt treatment for secondary bacterial infections, often superficial but can be serious and invasive with associated chronic morbidity and mortality. Post-scabetic itch and psychosocial stigma are typical sequelae of the scabies mite infestation. The early identification of patients with scabies and treatment of their contacts reduces community transmission. Although time consuming and labour intensive for caregivers, the implementation of appropriate treatment strategies usually results in prompt cure for the child and their contacts. Here, we provide a summary of treatments and recommendations for the management of paediatric scabies.

7.
Waste Manag ; 120: 650-658, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33243600

RESUMO

Solid waste management (SWM) is a key issue for sustainable development and environment protection, and waste collection and transportation (WCT) is one of the most important steps in managing solid waste. A well-designed SWM system with optimised location and capacity of waste transfer stations (WTSs) and final disposal facilities (FDFs) plays a critical role in waste management. However, uncertainties are inevitable in a general SWM system, which could involve in any stage of the waste management. In this paper, we propose to use the reliability analysis method to manage the uncertainties for the multiple-stage SWM system. Furthermore, an optimisation model is developed to maximise the reliability of SWM systems by optimising the allocation of waste treatment demand between facilities. We also generated an event-tree to analyse the failure mode of the whole system. Finally, a case study was undertaken in Hong Kong to demonstrate the effectiveness of the methodology. The case study results indicate that the proposed method can: (i) estate the risk level of a SWM system, (ii) provide a solution to improve the system reliability or reduce the risk level, (iii) analyse the potential contributions of different policies on the reliability index, (iv) identify the critical facilities in a SWM system.


Assuntos
Eliminação de Resíduos , Gerenciamento de Resíduos , Hong Kong , Reprodutibilidade dos Testes , Resíduos Sólidos
8.
Waste Manag ; 119: 1-10, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33032153

RESUMO

Disaster waste clean-up after large disasters is one of the core activities at the recovery stage of disaster management, which aims to restoring the normal functioning of the disaster affected area. In this paper we considered a waste clean-up system consists of (i) demolition operation, (ii) collection of waste from customer nodes to temporary disaster waste management sites (TDWMSs), (iii) processing at TDWMSs, and (iv) transportation of the waste to final disposal sites in the recovery of disasters. A multi-objective mixed integer programming model is developed to minimise the total clean-up cost and time. Three different approaches are developed to solve the problem, which are tested with artificial instances and a real case study. Results of artificial instances indicate that the models developed can be used to obtain close to optimal solutions within an acceptable computing time. Results of the case study can facilitate the decision-makers to develop the waste clean-up with minimised total cost and clean-up time by selecting the right location of TDWMSs and setting up the proper waste clean-up schedule.


Assuntos
Desastres , Eliminação de Resíduos , Gerenciamento de Resíduos , Meios de Transporte
9.
Plant Soil ; 457(1): 25-41, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33268909

RESUMO

AIM: Magnesium (Mg) deficiency (known as grass tetany) is a serious metabolic disorder that affects grazing ruminants. We tested whether Mg-fertiliser can increase Mg concentration of Italian ryegrasses (Lolium multiflorum L.) including a cultivar (cv. Bb2067; 'Magnet'), bred to accumulate larger concentrations of Mg. METHODS: Under controlled environment (CE) conditions, three cultivars (cv. Bb2067, cv. Bb2068, cv. RvP) were grown in low-nutrient compost at six fertiliser rates (0-1500 µM MgCl2.6H2O). Under field conditions, the three cultivars in the CE condition and cv. Alamo were grown at two sites, and four rates of MgSO4 fertiliser application rates (0-200 kg ha-1 MgO). Multiple grass cuts were taken over two-years. RESULTS: Grass Mg concentration increased with increasing Mg-fertiliser application rates in all cultivars and conditions. Under field conditions, cv. Bb2067 had 11-73% greater grass Mg concentration and smaller forage tetany index (FTI) than other cultivars across the Mg-fertiliser application rates, sites and cuts. Grass dry matter (DM) yield of cv. Bb2067 was significantly (p < 0.05) smaller than cv. Alamo. The effect of Mg-fertiliser rate on DM yield was not significant (p ≥ 0.05). CONCLUSIONS: Biofortification of grass with Mg through breeding and agronomy can improve the forage Mg concentration for grazing ruminants, even in high-growth spring grass conditions when hypomagnesaemia is most prevalent. Response to agronomic biofortification varied with cultivar, Mg-fertiliser rate, site and weather. The cost:benefit of these approaches and farmer acceptability, and the impact on cattle and sheep grazing on grasses biofortified with Mg requires further investigation.

10.
J Vasc Interv Radiol ; 31(5): 795-800, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32359526

RESUMO

From 2015 to 2019, 9 patients underwent ultrasound-guided intranodal lymphangiography for the treatment of a chyle leak following thoracic outlet decompression surgery. Chyle leaks were identified by Lipiodol (Guerbet, Roissy, France) extravasation near the left supraclavicular surgical bed in all patients. The technical success rate of thoracic duct embolization was 67% (6 of 9), including fluoroscopic transabdominal antegrade access (n = 4) and ultrasound-guided retrograde access in the left neck (n = 2). Clinical success was achieved in 89% of patients (8 of 9). The mean interval from lymphangiography to drain removal was 6.6 days (range, 4-18 d). No patients had a chyle leak recurrence during clinical follow-up (mean, 304 d).


Assuntos
Quilo/diagnóstico por imagem , Descompressão Cirúrgica/efeitos adversos , Embolização Terapêutica , Linfografia , Ducto Torácico/diagnóstico por imagem , Síndrome do Desfiladeiro Torácico/cirurgia , Adulto , Embolização Terapêutica/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Ducto Torácico/lesões , Síndrome do Desfiladeiro Torácico/diagnóstico por imagem , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
11.
Nat Protoc ; 15(1): 181, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31705126

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

12.
Nat Protoc ; 14(11): 3033-3058, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31628445

RESUMO

V2a interneurons are located in the hindbrain and spinal cord, where they provide rhythmic input to major motor control centers. Many of the phenotypic properties and functions of excitatory V2a interneurons have yet to be fully defined. Definition of these properties could lead to novel regenerative therapies for traumatic injuries and drug targets for chronic degenerative diseases. Here we describe how to produce V2a interneurons from mouse and human pluripotent stem cells (PSCs), as well as strategies to characterize and mature the cells for further analysis. The described protocols are based on a sequence of small-molecule treatments that induce differentiation of PSCs into V2a interneurons. We also include a detailed description of how to phenotypically characterize, mature, and freeze the cells. The mouse and human protocols are similar in regard to the sequence of small molecules used but differ slightly in the concentrations and durations necessary for induction. With the protocols described, scientists can expect to obtain V2a interneurons with purities of ~75% (mouse) in 7 d and ~50% (human) in 20 d.


Assuntos
Interneurônios/citologia , Neurogênese , Células-Tronco Pluripotentes/citologia , Animais , Técnicas de Cultura de Células/métodos , Linhagem Celular , Humanos , Camundongos
13.
J Chem Phys ; 150(20): 204109, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31153158

RESUMO

Polymer self-consistent field theory techniques are used to derive quantum density functional theory without the use of the theorems of density functional theory. Instead, a free energy is obtained from a partition function that is constructed directly from a Hamiltonian so that the results are, in principle, valid at finite temperatures. The main governing equations are found to be a set of modified diffusion equations, and the set of self-consistent equations are essentially identical to those of a ring polymer system. The equations are shown to be equivalent to Kohn-Sham density functional theory and to reduce to classical density functional theory, each under appropriate conditions. The obtained noninteracting kinetic energy functional is, in principle, exact but suffers from the usual orbital-free approximation of the Pauli exclusion principle in addition to the exchange-correlation approximation. The equations are solved using the spectral method of polymer self-consistent field theory, which allows the set of modified diffusion equations to be evaluated for the same computational cost as solving a single diffusion equation. A simple exchange-correlation functional is chosen, together with a shell-structure-based Pauli potential, in order to compare the ensemble average electron densities of several isolated atom systems to known literature results. The agreement is excellent, justifying the alternative formalism and numerical method. Some speculation is provided on considering the timelike parameter in the diffusion equations, which is related to temperature, as having dimensional significance, and thus picturing pointlike quantum particles instead as nonlocal, polymerlike, threads in a higher dimensional thermal-space. A consideration of the double-slit experiment from this point of view is speculated to provide results equivalent to the Copenhagen interpretation. Thus, the present formalism may be considered as a type of "pilot-wave," realist, perspective on density functional theory.

14.
Surg Laparosc Endosc Percutan Tech ; 29(6): 441-446, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31135712

RESUMO

BACKGROUND: Drugs used for sedation/analgesia during gastrointestinal (GI) endoscopy, including midazolam, fentanyl, and propofol, result in short-term, reversible decline in cognitive function. This prospective cohort trial aimed to identify the sedative/analgesic regimen associated with the least impairment of cognition at the time of discharge. METHODS: Patients undergoing elective GI endoscopy were included. Patients investigated at the Prince of Wales Hospital, Sydney, received midazolam/fentanyl (M/F), whereas patients investigated at the Prince of Wales Private Hospital, Sydney, received midazolam/fentanyl/propofol (M/F/P) or midazolam/propofol (M/P). Patients underwent a computerized neurocognitive test, the CogState Brief Battery, before sedation and at discharge. RESULTS: Patients in the M/F group who received gastroscopy (n=22) were administered midazolam 3.36 mg (±0.79 mg) and fentanyl 61.36 µg (±16.77 µg), those who received colonoscopy (n=50) were administered midazolam 3.98 mg (±1.06 mg) and fentanyl 74.50 µg (±24.48 µg), and those who received gastroscopy/colonoscopy (n=28) were administered midazolam 4.82 mg (±1.41 mg) and fentanyl 94.64 µg (±24.35 µg). Patients in the M/F/P group who received colonoscopy (n=45) were administered midazolam 2.77 mg (±0.55 mg), fentanyl 45.11 µg (±25.78 µg), and propofol 148.64 mg (±57.65 mg), and those who received gastroscopy/colonoscopy (n=36) were administered midazolam 2.64 mg (±0.472 mg), fentanyl 35.28 µg (±19.16 µg), and propofol 168.06 mg (±60.75 mg). Nineteen patients in the M/P group who received gastroscopy (n=19) were administered midazolam 2.37 mg (±0.04 mg) and propofol 13.68 mg (±37.74 mg). Neurocognitive scores were significantly lower in the postprocedure test compared with baseline scores for detection, identification, and one card learning (P<0.001). Postprocedure detection test scores were significantly impaired in the M/F group compared with the M/F/P and M/P groups. Predictors of poorer neurocognitive function were midazolam dosage >3 mg (P<0.006) and fentanyl dosage >50 µg (P<0.009). CONCLUSION: The use of propofol in GI endoscopy allows for less exposure to midazolam and fentanyl and is associated with improved cognition at the time of discharge.


Assuntos
Cognição/fisiologia , Endoscopia Gastrointestinal/métodos , Fentanila/farmacologia , Midazolam/farmacologia , Dor/prevenção & controle , Propofol/farmacologia , Analgésicos Opioides/farmacologia , Cognição/efeitos dos fármacos , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Hipnóticos e Sedativos/farmacologia , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Estudos Prospectivos
15.
Waste Manag ; 84: 383-393, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30470631

RESUMO

The condition of road networks which connect disaster affected areas and final disposal sites has a critical role in the management of disaster waste. In this paper, we present a two-stage framework to estimate the overall reliability and failure modes of a disaster waste management system considering the reliability of each route involved in the road network. In the first stage, first order reliability method and Ditlevsen bounds are applied to estimate system reliability. In the second stage, an event tree approach is implemented to analyse the failure modes of the system. The methodology is demonstrated with an artificial case study considering three different scales of disasters. The results obtained from the case study can provide information to decision makers regarding the priority of the routes in the system and the most likely failure mode.


Assuntos
Desastres , Gerenciamento de Resíduos , Reprodutibilidade dos Testes
16.
Soft Matter ; 14(22): 4603-4614, 2018 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-29786729

RESUMO

A variant of the Sanchez-Lacombe equation of state is applied to several polymers, blowing agents, and saturated mixtures of interest to the polymer foaming industry. These are low-density polyethylene-carbon dioxide and polylactide-carbon dioxide saturated mixtures as well as polystyrene-carbon dioxide-dimethyl ether and polystyrene-carbon dioxide-nitrogen ternary saturated mixtures. Good agreement is achieved between theoretically predicted and experimentally determined solubilities, both for binary and ternary mixtures. Acceptable agreement with swelling ratios is found with no free parameters. Up-to-date pure component Sanchez-Lacombe characteristic parameters are provided for carbon dioxide, dimethyl ether, low-density polyethylene, nitrogen, polylactide, linear and branched polypropylene, and polystyrene. Pure fluid low-density polyethylene and nitrogen parameters exhibit more moderate success while still providing acceptable quantitative estimations. Mixture estimations are found to have more moderate success where pure components are not as well represented. The Sanchez-Lacombe equation of state is found to correctly predict the anomalous reversal of solubility temperature dependence for low critical point fluids through the observation of this behaviour in polystyrene nitrogen mixtures.

17.
Biomaterials ; 162: 208-223, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29459311

RESUMO

One reason for the lack of regeneration, and poor clinical outcomes, following central nervous system (CNS) injury is the formation of a glial scar that inhibits new axon growth. In addition to forming the glial scar, astrocytes have been shown to be important for spontaneous SCI recovery in rodents, suggesting some astrocyte populations are pro-regenerative, while others are inhibitory following injury. In this work, the effect of implanting hyaluronic acid (HA) hydrogels containing extracellular matrix (ECM) harvested from mouse embryonic stem cell (mESC)-derived astrocytes on histologic outcomes following SCI in rats was explored. In addition, the ability of HA hydrogels with and without ECM to support the transplantation of mESC-derived V2a interneurons was tested. The incorporation of ECM harvested from protoplasmic (grey matter) astrocytes, but not ECM harvested from fibrous (white matter) astrocytes, into hydrogels was found to reduce the size of the glial scar, increase axon penetration into the lesion, and reduce macrophage/microglia staining two weeks after implantation. HA hydrogels were also found to support transplantation of V2a interneurons and the presence of these cells caused an increase in neuronal processes both within the lesion and in the 500 µm surrounding the lesion. Overall, protoplasmic mESC-derived astrocyte ECM showed potential to treat CNS injury. In addition, ECM:HA hydrogels represent a novel scaffold with beneficial effects on histologic outcomes after SCI both with and without cells.


Assuntos
Matriz Extracelular/química , Ácido Hialurônico/química , Hidrogéis/química , Traumatismos da Medula Espinal/cirurgia , Animais , Astrócitos/efeitos dos fármacos , Células-Tronco Embrionárias/citologia , Células-Tronco Embrionárias/fisiologia , Interneurônios/efeitos dos fármacos , Camundongos , Regeneração Nervosa/efeitos dos fármacos , Ratos , Engenharia Tecidual/métodos
18.
Waste Manag ; 78: 31-42, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32559916

RESUMO

The management of disaster waste is one of the most critical tasks associated with recovery after a disaster. Having a general idea of the required capacity, cost and target clean-up time while considering the uncertainties involved in the system before the detailed plan of a disaster waste clean-up system is significant. Reliability analysis is a method to judge the performance of a system and deal with uncertainties in the system. Evaluating the reliability of the system, which can indicate the possibility to complete the clean-up within the target time and cost, and optimising the system to maximise the reliability to provide information to decision-makers regarding the capacity, cost and time required to finish the clean-up is the purpose of this paper. A mathematical model is developed applying the First Order Reliability Method (FORM) to address the problem. Additionally, a non-linear optimisation model is developed to improve the reliability of the disaster waste clean-up system with consideration of the total cost and clean-up time constraints, and solved using a Genetic Algorithm. The proposed models are implemented to solve a case study in Queensland, Australia. It is shown that the models have the capability of maximising the reliability and minimising the total clean-up costs by optimising the arrangement of vehicles during the clean-up process.

19.
Biomed Mater ; 13(2): 024104, 2018 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-29186011

RESUMO

Trauma to either the central or peripheral nervous system (PNS) often leads to significant loss of function and disability in patients. This high rate of long-term disability is due to the overall limited regenerative potential of nervous tissue, even though the PNS has more regenerative potential than the central nervous system (CNS). The supporting glial cells in the periphery, Schwann cells, are part of the reason for the improved recovery observed in the PNS. In the CNS, the glial populations, astrocytes and oligodendrocytes (OLs), do not have as much potential to promote regeneration and are at times inhibitory to neuronal growth. In particular, the inhibitory roles astrocytes play following trauma has led to a historical focus on neurons and OLs instead of astrocytes. Recently, this focus has shifted as new, regenerative astrocyte phenotypes have been described. From these observations, glial cells clearly play critical roles in native recovery pathways in both the CNS and PNS. This makes the ability to manipulate both transplanted and native glial cell phenotypes a potentially successful strategy to improve nerve injury outcomes. This review focuses on factors that cause glial cells to adopt repair phenotypes and biomaterials that manipulate and/or harness these glial phenotypes.


Assuntos
Materiais Biocompatíveis/química , Regeneração Nervosa/fisiologia , Neuroglia/metabolismo , Traumatismos do Sistema Nervoso/terapia , Animais , Astrócitos/citologia , Axônios/fisiologia , Linhagem da Célula , Sistema Nervoso Central , Humanos , Camundongos , Bainha de Mielina/química , Neurônios/fisiologia , Sistema Nervoso Periférico , Fenótipo , Ratos , Regeneração , Células de Schwann/fisiologia
20.
Stem Cells Dev ; 26(22): 1597-1611, 2017 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-28851266

RESUMO

Central nervous system injury often leads to functional impairment due, in part, to the formation of an inhibitory glial scar following injury that contributes to poor regeneration. Astrocytes are the major cellular components of the glial scar, which has led to the belief that they are primarily inhibitory following injury. Recent work has challenged this by demonstrating that some astrocytes are required for spinal cord regeneration and astrocytic roles in recovery depend on their phenotype. In this work, two mixed populations containing primarily either fibrous or protoplasmic astrocytes were derived from mouse embryonic stem cells (mESCs). Motoneuron and V2a interneuron growth on live cultures, freeze-lysed cultures, or decellularized extracellular matrix (ECM) from astrocytes were assessed. Both neuronal populations were found to extend significantly longer neurites on protoplasmic-derived substrates than fibrous-derived substrates. Interestingly, neurons extended longer neurites on protoplasmic-derived ECM than fibrous-derived ECM. ECM proteins were compared with in vivo astrocyte expression profiles, and it was found that the ESC-derived ECMs were enriched for astrocyte-specific proteins. Further characterization revealed that protoplasmic ECM had significantly higher levels of axon growth promoting proteins, while fibrous ECM had significantly higher levels of proteins that inhibit axon growth. Supporting this observation, knockdown of spondin-1 improved neurite growth on fibrous ECM, while laminin α5 and γ1 knockdown decreased neurite growth on protoplasmic ECM. These methods allow for scalable production of specific astrocyte subtype-containing populations with different neuronal growth support capacities, and can be used for further studies of the functional importance of astrocyte heterogeneity.


Assuntos
Astrócitos/citologia , Células-Tronco Embrionárias/citologia , Regeneração Nervosa/fisiologia , Neurônios/citologia , Animais , Matriz Extracelular/metabolismo , Proteína Glial Fibrilar Ácida/metabolismo , Camundongos , Neuritos/fisiologia , Neurogênese/fisiologia , Neuroglia/citologia , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/terapia
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