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1.
Nat Commun ; 11(1): 5196, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-33060592

RESUMO

Pericytes play essential roles in blood-brain barrier (BBB) integrity and dysfunction or degeneration of pericytes is implicated in a set of neurological disorders although the underlying mechanism remains largely unknown. However, the scarcity of material sources hinders the application of BBB models in vitro for pathophysiological studies. Additionally, whether pericytes can be used to treat neurological disorders remains to be elucidated. Here, we generate pericyte-like cells (PCs) from human pluripotent stem cells (hPSCs) through the intermediate stage of the cranial neural crest (CNC) and reveal that the cranial neural crest-derived pericyte-like cells (hPSC-CNC PCs) express typical pericyte markers including PDGFRß, CD146, NG2, CD13, Caldesmon, and Vimentin, and display distinct contractile properties, vasculogenic potential and endothelial barrier function. More importantly, when transplanted into a murine model of transient middle cerebral artery occlusion (tMCAO) with BBB disruption, hPSC-CNC PCs efficiently promote neurological functional recovery in tMCAO mice by reconstructing the BBB integrity and preventing of neuronal apoptosis. Our results indicate that hPSC-CNC PCs may represent an ideal cell source for the treatment of BBB dysfunction-related disorders and help to model the human BBB in vitro for the study of the pathogenesis of such neurological diseases.


Assuntos
Isquemia Encefálica/metabolismo , Pericitos/metabolismo , Recuperação de Função Fisiológica/fisiologia , Acidente Vascular Cerebral/metabolismo , Animais , Barreira Hematoencefálica/metabolismo , Isquemia Encefálica/patologia , Diferenciação Celular/genética , Infarto da Artéria Cerebral Média , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Crista Neural/metabolismo , Células-Tronco Pluripotentes/metabolismo , Receptor beta de Fator de Crescimento Derivado de Plaquetas/metabolismo , Recuperação de Função Fisiológica/genética , Acidente Vascular Cerebral/patologia , Transcriptoma
2.
Science ; 370(6512)2020 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-33004487

RESUMO

Injuries to the central nervous system (CNS) are inefficiently repaired. Resident neural stem cells manifest a limited contribution to cell replacement. We have uncovered a latent potential in neural stem cells to replace large numbers of lost oligodendrocytes in the injured mouse spinal cord. Integrating multimodal single-cell analysis, we found that neural stem cells are in a permissive chromatin state that enables the unfolding of a normally latent gene expression program for oligodendrogenesis after injury. Ectopic expression of the transcription factor OLIG2 unveiled abundant stem cell-derived oligodendrogenesis, which followed the natural progression of oligodendrocyte differentiation, contributed to axon remyelination, and stimulated functional recovery of axon conduction. Recruitment of resident stem cells may thus serve as an alternative to cell transplantation after CNS injury.


Assuntos
Células-Tronco Neurais/fisiologia , Neurogênese/fisiologia , Oligodendroglia/fisiologia , Regeneração da Medula Espinal/fisiologia , Animais , Astrócitos/fisiologia , Axônios/fisiologia , Linhagem da Célula , Epêndima/citologia , Epêndima/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Neurogênese/genética , Fator de Transcrição 2 de Oligodendrócitos/metabolismo , Oligodendroglia/citologia , Recuperação de Função Fisiológica/genética , Recuperação de Função Fisiológica/fisiologia , Remielinização/genética , Remielinização/fisiologia , Análise de Célula Única , Traumatismos da Medula Espinal/fisiopatologia , Regeneração da Medula Espinal/genética
4.
Artigo em Inglês | MEDLINE | ID: mdl-32872251

RESUMO

Sixteen female soccer players (age = 20.19 ± 1.52 years; body mass = 56.52 ± 4.95 kg; body height = 164.81 ± 4.21 cm) with no history of lower extremity injury participated in the study. The Biodex SD Balance system was used to determine the non-dominant single-leg stability. In anaerobic exercise, each subject performed four maximal cycling efforts against a resistance equivalent to 0.075 kg/body mass for 30 s with three-minute rest intervals. In aerobic exercise, subjects performed the Bruce protocol on a motorized treadmill. After each exercise, subjects subsequently performed a single-leg stability test and then repeated the same test for four times with five-minute passive rest periods. In accordance with the results, it was found that the impairment observed right after the aerobic loading was higher (p < 0.001) compared to the anaerobic one. However, the time-related deterioration in both aerobic and anaerobic loadings was similar. The B-pre value was lower than Bpost and B5 (p < 0.01) and B10 (p < 0.05) in both conditions. Subjects could reach the initial balance level at B15 after aerobic and anaerobic loadings. The lactate level did not reach resting value even after 20 min of both fatigue protocols. Although the fatigue after aerobic and aerobic exercise negatively affects a single-leg dynamic balance level, single leg balance ability returns to the baseline status after 10 min of passive recovery duration.


Assuntos
Limiar Anaeróbio/fisiologia , Exercício Físico/fisiologia , Fadiga , Equilíbrio Postural/fisiologia , Recuperação de Função Fisiológica/fisiologia , Futebol/fisiologia , Adulto , Anaerobiose , Teste de Esforço , Feminino , Humanos
5.
Stroke ; 51(10): 3129-3132, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32867599

RESUMO

BACKGROUND AND PURPOSE: We analyzed differences in 90-day poststroke outcomes between Mexican Americans born in the United States (nonimmigrant) compared with those born outside the United States (immigrant). METHODS: We performed a retrospective analysis of prospective data from the population-based Brain Attack Surveillance in Corpus Christi project. We identified stroke cases from 2008 to 2016 and quantified functional, cognitive, and neurological outcomes. Associations between outcome scores and immigration status were analyzed using weighted linear regression models. RESULTS: Eighty-three Mexican American stroke cases (n=935) were immigrants, and 852 stroke cases were nonimmigrants. Average length of stay in the United States for immigrants was 47 years. Immigrants were older (69 versus 66 years), more likely men (60% versus 49%), had less education on average, and were more likely to have atrial fibrillation compared with nonimmigrants. No differences in other comorbidities existed between groups. After adjustment for confounders, immigrants had better functional outcomes (activities of daily living/instrumental activities of daily living; mean difference, -0.22; P=0.02; 1-4, higher scores worse) and no difference in neurological outcomes (log-National Institutes of Health Stroke Scale; mean difference, -0.15; P=0.15; 0-44, higher scores worse) or cognitive outcomes (3 Mini-Mental State Examination; mean difference, -0.79; P=0.64; 0-100, lower scores worse). CONCLUSIONS: Long-term Mexican American immigrants in this community display better stroke functional outcomes than nonimmigrant Mexican Americans and comparable neurological and cognitive outcomes.


Assuntos
Atividades Cotidianas , Recuperação de Função Fisiológica/fisiologia , Acidente Vascular Cerebral/fisiopatologia , Fatores Etários , Idoso , Escolaridade , Emigrantes e Imigrantes , Feminino , Humanos , Masculino , Americanos Mexicanos , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Estados Unidos
6.
Stroke ; 51(10): 3095-3106, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32933419

RESUMO

BACKGROUND AND PURPOSE: Poststroke tissue repair, comprised of macrophage-mediated clearance of myelin debris and pericyte-mediated fibrotic response within the infarct area, is an important process for functional recovery. Herein, we investigated the reciprocal interaction between pericytes and macrophages during poststroke repair and functional recovery. METHODS: We performed a permanent middle cerebral artery occlusion in both wild-type and pericyte-deficient PDGFRß (platelet-derived growth factor receptor ß) heterozygous knockout (Pdgfrb+/-) mice and compared histological changes and neurological functions between the 2 groups. We also examined the effects of conditioned medium harvested from cultured pericytes, or bone marrow-derived macrophages, on the functions of other cell types. RESULTS: Localization of PDGFRß-positive pericytes and F4/80-positive macrophages was temporally and spatially very similar following permanent middle cerebral artery occlusion. Intrainfarct accumulation of macrophages was significantly attenuated in Pdgfrb+/- mice. Intrainfarct pericytes expressed CCL2 (C-C motif ligand 2) and CSF1 (colony stimulating factor 1), both of which were significantly lower in Pdgfrb+/- mice. Cultured pericytes expressed Ccl2 and Csf1, both of which were significantly increased by PDGF-BB and suppressed by a PDGFRß inhibitor. Pericyte conditioned medium significantly enhanced migration and proliferation of bone marrow-derived macrophages. Poststroke clearance of myelin debris was significantly attenuated in Pdgfrb+/- mice. Pericyte conditioned medium promoted phagocytic activity in bone marrow-derived macrophages, also enhancing both STAT3 (signal transducer and activator of transcription 3) phosphorylation and expression of scavenger receptors, Msr1 and Lrp1. Macrophages processing myelin debris produced trophic factors, enhancing PDGFRß signaling in pericytes leading to the production of ECM (extracellular matrix) proteins and oligodendrogenesis. Functional recovery was significantly attenuated in Pdgfrb+/- mice, parallel with the extent of tissue repair. CONCLUSIONS: A reciprocal interaction between pericytes and macrophages is important for poststroke tissue repair and functional recovery.


Assuntos
Infarto da Artéria Cerebral Média/metabolismo , Macrófagos/metabolismo , Pericitos/metabolismo , Recuperação de Função Fisiológica/fisiologia , Acidente Vascular Cerebral/metabolismo , Cicatrização/fisiologia , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Meios de Cultivo Condicionados , Infarto da Artéria Cerebral Média/patologia , Macrófagos/patologia , Camundongos , Camundongos Knockout , Pericitos/patologia , Receptor beta de Fator de Crescimento Derivado de Plaquetas/genética , Receptor beta de Fator de Crescimento Derivado de Plaquetas/metabolismo , Acidente Vascular Cerebral/patologia
7.
Stroke ; 51(10): 3169-3173, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32951539

RESUMO

The repair and recovery of the brain after stroke is a field that is emerging in its preclinical science and clinical trials. However, recent large, multicenter clinical trials have been negative, and conflicting results emerge on biological targets in preclinical studies. The coalescence of negative clinical translation and confusion in preclinical studies raises the suggestion that perhaps the field of stroke recovery faces a fate similar to stroke neuroprotection, with interesting science ultimately proving difficult to translate to the clinic. This review highlights improvements in 4 areas of the stroke neural repair field that should reorient the field toward successful clinical translation: improvements in rodent genetic models of stroke recovery, consideration of the biological target in stroke recovery, stratification in clinical trials, and the use of appropriate clinical trial end points.


Assuntos
Encéfalo/fisiopatologia , Plasticidade Neuronal/fisiologia , Recuperação de Função Fisiológica/fisiologia , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral/fisiopatologia , Animais , Modelos Animais de Doenças , Humanos
9.
Am Surg ; 86(9): 1124-1128, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32841047

RESUMO

INTRODUCTION: Traumatic brain injury (TBI) remains a significant cause of morbidity and mortality. The purpose of this study is to examine outcomes after discharge and identify factors from the index admission that may contribute to long-term mortality. METHODS: The study population is composed of patients who survived to discharge from a previously published study examining TBI. Demographics, injury severity, and length of stay were abstracted from the index study. Phone surveys of surviving patients were performed to evaluate each patient's Glasgow Outcome Scale-Extended (GOSE). Patients who were deceased at the time of the survey were compared with those who were alive. RESULTS: 1615 patients were alive at the end of the first study period and 211 (13%) comprised the study population. Overall, the median age was 54 years, and the majority were male (74%). The median time to follow-up was 80 months. The population was severely injured, with a median injury severity score (ISS) of 25 and a median head abbreviated injury score (AIS) of 4. Overall mortality was 57%. The group that survived at the time of the survey was younger, more injured, less likely to have received beta-blockers (BB) during the index admission, and had a longer time to follow-up. After adjusting for ISS, age, base deficit, and BB, age was the only variable predictive of mortality (HR 1.03; HL 1.02-1.04). CONCLUSION: Despite being more severely injured, younger patients were more likely to survive to follow-up. Further investigation is needed to determine if aggressive care in older TBI patients in the acute phase leads to good long-term outcomes.


Assuntos
Lesões Encefálicas Traumáticas/fisiopatologia , Recuperação de Função Fisiológica/fisiologia , Centros de Traumatologia , Adulto , Lesões Encefálicas Traumáticas/diagnóstico , Lesões Encefálicas Traumáticas/mortalidade , Feminino , Seguimentos , Humanos , Escala de Gravidade do Ferimento , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Fatores de Tempo , Estados Unidos/epidemiologia
10.
PLoS One ; 15(8): e0237047, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32745086

RESUMO

Deep prosthetic hip infection is a devastating complication of hip replacement surgery, and treatment often involves multiple revision surgeries with antibiotic chemotherapy to control the infection. The aim of this study was to explore patients' experiences of early and longer-term recovery after one-stage or two-stage revision with an excised hip, a temporary cement spacer or a custom-made articulating spacer. We interviewed 32 participants taking part in a surgical trial at two time points (2-4 months and 18 months) following one- or two-stage revision surgery. The analytic approach was inductive using the constant comparative method to generate themes from the data. Participants' early recovery after revision was characterised by a long hospital stay with burdensome antibiotics and limited physiotherapy provision. Participants undergoing two-stage revision with an excised hip or a cement spacer described severe mobility restrictions which affected all aspects of their lives, while those undergoing one-stage revision, or two-stage revision with an articulating spacer were more mobile and independent, with some limitations. Participants with a cement spacer also reported more pain than other treatment groups, while those with an articulating spacer appeared to perceive that their recovery was slow. At 18 months, participants in all groups described both improvements and losses in mobility and functional ability. Participants in all treatment groups expressed considerable emotional resilience during recovery from revision, which may be linked to opportunities to talk with the trial personnel. Participants identified the need for better information and psychological and physical support. Experience of recovery differs after one- and two-stage revision, and further in relation to the use of spacers. Mobility, function, independence and pain are important aspects of recovery which affect all aspects of day-to-day life. Increased information and more opportunities to talk and share experiences may provide psychological support during recovery.


Assuntos
Infecções Relacionadas à Prótese/psicologia , Recuperação de Função Fisiológica/fisiologia , Reoperação/psicologia , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Artrite Infecciosa/tratamento farmacológico , Artroplastia de Quadril/efeitos adversos , Cimentos para Ossos/uso terapêutico , Feminino , Humanos , Articulações/cirurgia , Masculino , Pessoa de Meia-Idade , Próteses e Implantes/efeitos adversos , Infecções Relacionadas à Prótese/etiologia , Pesquisa Qualitativa , Reoperação/efeitos adversos
11.
PLoS One ; 15(8): e0221668, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32776927

RESUMO

BACKGROUND: Animal models of brain recovery identify the first days after lesioning as a time of great flux in sensorimotor function and physiology. After rodent motor system lesioning, daily skill training in the less affected forelimb reduces skill acquisition in the more affected forelimb. We asked whether spontaneous human motor behaviors of the less affected upper extremity (UE) early after stroke resemble the animal training model, with the potential to suppress clinical recovery. METHODS: This prospective observational study used a convenience sample of patients (n = 25, mean 4.5 ±1.8) days after stroke with a wide severity range; Controls were hospitalized for non-neurological conditions (n = 12). Outcome measures were Accelerometry, Upper-Extremity Fugl-Meyer (UEFM), Action Research Arm Test (ARAT), Shoulder Abduction/ Finger Extension Test (SAFE), NIH Stroke Scale (NIHSS). RESULTS: Accelerometry indicated total paretic UE movement was reduced compared to controls, primarily due to a 44% reduction of bilateral UE use. Unilateral paretic movement was unchanged. Thus, movement shifted early after stroke; bilateral use was reduced and unilateral use of the non-paretic UE was increased by 77%. Low correlations between movement time and motor performance prompted an exploratory factor analysis (EFA) revealing a 2-component solution; motor performance tests load on one component (motor performance) whereas accelerometry-derived variables load on a second orthogonal component (quantity of movement). CONCLUSIONS: Early after stroke, spontaneous overall UE movement is reduced, and movement shifts to unilateral use of the non-paretic UE. Two mechanisms that could influence motor recovery may already be in place 4.5 ± 1.8 days post stroke: (1) the overuse of the less affected UE, which could set the stage for learned non-use and (2) skill acquisition in the non-paretic limb that could impede recovery. Accurate UE motor assessment requires two independent constructs: motor performance and quantity of movement. These findings provide opportunities and measurement methods for studies to develop new behaviorally-based stroke recovery treatments that begin early after onset.


Assuntos
Atividade Motora/fisiologia , Reabilitação do Acidente Vascular Cerebral/métodos , Acidente Vascular Cerebral/fisiopatologia , Acelerometria/métodos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Destreza Motora/fisiologia , Movimento/fisiologia , Avaliação de Resultados em Cuidados de Saúde , Paresia/fisiopatologia , Paresia/terapia , Estudos Prospectivos , Recuperação de Função Fisiológica/fisiologia , Fatores de Tempo , Estados Unidos , Extremidade Superior/fisiologia
12.
Life Sci ; 258: 118214, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32768585

RESUMO

Large numbers of rodents are often used in the study of disease progression and in the evaluation of its potential treatments. To avoid subjective observation and to minimize home cage interference, we developed a computerized home cage monitoring system (HCMS100) based on a standard cage rack adapted with a single laser beam and a detector mounted on each cage, enabling to monitor mice movements based on laser beam interruptions. This retrofit system provided continuous and uninterrupted monitoring of spontaneous movement of a group of mice in a home cage. Validity was evaluated using disease state induced by LPS modelling bacterial infection and by influenza virus. RESULTS: Spontaneous activity of different number of mice (2-8) per cage showed the expected circadian rhythm with increased activity during the night, and its extent dependent on the number of mice in the cage. Females and males show similar circadian rhythm. Intranasal LPS administration and pulmonary infection with live influenza virus resulted in major reduction of mice activity along disease progression. Increase in activity over time was a good indicator of the recovery process from both LPS exposure and the flu infection. CONCLUSIONS: HCMS100 was shown to be a reliable, inexpensive, easy to use system that requires no changes in the common housing of various experimental animals (mice, hamsters, rats etc.). With minimal intervention, HCMS100 provides a continuous record of group activity with clear pattern of circadian rhythm, allowing long term recording of home cage activity even in restricted access environments.


Assuntos
Progressão da Doença , Abrigo para Animais , Lipopolissacarídeos/toxicidade , Infecções por Orthomyxoviridae/fisiopatologia , Orthomyxoviridae , Recuperação de Função Fisiológica/fisiologia , Animais , Ritmo Circadiano/fisiologia , Feminino , Abrigo para Animais/tendências , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Infecções por Orthomyxoviridae/psicologia , Recuperação de Função Fisiológica/efeitos dos fármacos
13.
Medicine (Baltimore) ; 99(28): e20886, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32664081

RESUMO

Due to the great difficulty in being preserved in site for the variable positions, the inferior parathyroid glands were advised to being routinely autotransplanted to prevent permanent hypoparathyroidism. The aim of this study was to compare the performance in the function of the superior parathyroid glands preserved in site with that of the inferior parathyroid glands preserved in site.We conducted a retrospective study including patients who underwent thyroid surgery for papillary thyroid carcinoma at our department between January 2014 and June 2018. According to the number and original position of the autoplastic parathyroid gland(s), patients were divided into group 1 (1 superior parathyroid gland), group 2 (1 inferior parathyroid glands), group 3 (1 superior parathyroid gland and 1 inferior parathyroid gland) and group 4 (2 inferior parathyroid glands). The postoperative complications and serum parathyroid hormone and calcium were analyzed.A total of 368 patients were included in the study, among them 27, 243, 40, and 58 patients were divided into group 1, group 2, group 3, and group 4, respectively. Compared with those in group 2, the serum parathyroid hormones were higher at 1 week (2.98 ±â€Š1.52 vs 2.42 ±â€Š0.89, P = .049) and 2 weeks (3.49 ±â€Š1.42 vs 2.8 ±â€Š0.81, P = .019) postoperatively in group 1. There was also significantly different in the serum parathyroid hormone at 2 weeks postoperatively between group 3 and group 4 (2.95 ±â€Š0.98 vs 2.58 ±â€Š0.82, P = .047).The inferior parathyroid glands preserved in site recover faster than the superior parathyroid glands preserved in site.


Assuntos
Glândulas Paratireoides/fisiologia , Glândulas Paratireoides/cirurgia , Câncer Papilífero da Tireoide/cirurgia , Glândula Tireoide/patologia , Transplante Autólogo/efeitos adversos , Adulto , Cálcio/sangue , Feminino , Humanos , Hipoparatireoidismo/prevenção & controle , Masculino , Pessoa de Meia-Idade , Glândulas Paratireoides/anatomia & histologia , Hormônio Paratireóideo/sangue , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Recuperação de Função Fisiológica/fisiologia , Estudos Retrospectivos , Transplante Autólogo/métodos
14.
Stroke ; 51(8): 2553-2557, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32611286

RESUMO

BACKGROUND AND PURPOSE: We aimed to delineate the determinants of the initial speed of infarct progression and the association of speed of infarct progression (SIP) with procedural and functional outcomes. METHODS: From a prospectively maintained stroke center registry, consecutive anterior circulation ischemic stroke patients with large artery occlusion, National Institutes of Health Stroke Scale score ≥4, and multimodal vessel, ischemic core, and tissue-at-risk imaging within 24 hours of onset were included. Initial SIP was calculated as ischemic core volume at first imaging divided by the time from stroke onset to imaging. RESULTS: Among the 88 patients, SIP was median 2.2 cc/h (interquartile range, 0-8.7), ranging most widely within the first 6 hours after onset. Faster SIP was positively independently associated with a low collateral score (odds ratio [OR], 3.30 [95% CI, 1.25-10.49]) and arrival by emergency medical services (OR, 3.34 [95% CI, 1.06-10.49]) and negatively associated with prior ischemic stroke (OR, 0.12 [95% CI, 0.03-0.50]) and coronary artery disease (OR, 0.32 [95% CI, 0.10-1.00]). Among the 67 patients who underwent endovascular thrombectomy, slower SIP was associated with a shift to reduced levels of disability at discharge (OR, 3.26 [95% CI, 1.02-10.45]), increased substantial reperfusion by thrombectomy (OR, 8.30 [95% CI, 0.97-70.87]), and reduced radiological hemorrhagic transformation (OR, 0.34 [95% CI, 0.12-0.94]). CONCLUSIONS: Slower SIP is associated with a high collateral score, prior ischemic stroke, and coronary artery disease, supporting roles for both collateral robustness and ischemic preconditioning in fostering tissue resilience to ischemia. Among patients undergoing endovascular thrombectomy, the speed of infarct progression is a major determinant of clinical outcome.


Assuntos
Isquemia Encefálica/diagnóstico por imagem , Progressão da Doença , Recuperação de Função Fisiológica/fisiologia , Acidente Vascular Cerebral/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/epidemiologia , Isquemia Encefálica/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Sistema de Registros , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/terapia , Fatores de Tempo , Resultado do Tratamento
15.
Stroke ; 51(8): 2514-2525, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32640942

RESUMO

BACKGROUND AND PURPOSE: Stroke is a major cause of chronic neurological disability. There is considerable interest in understanding how acute transcriptome changes evolve into subacute and chronic patterns that facilitate or limit spontaneous recovery. Here we mapped longitudinal changes in gene expression at multiple time points after stroke in mice out to 6 months. METHODS: Adult C57BL/6 mice were subjected to transient middle cerebral artery occlusion. Longitudinal transcriptome levels were measured at 10 time points after stroke from acute to recovery phases of ischemic stroke. Localization and the number of mononuclear phagocytes were determined in the postischemic brain. Whole-mount brain imaging was performed in asplenic mice receiving GFP+ (green fluorescent protein)-tagged splenocytes. RESULTS: Sustained stroke-induced mRNA abundance changes were observed in both hemispheres with 2989 ipsilateral and 822 contralateral genes significantly perturbed. In the hemisphere ipsilateral to the infarct, genes associated with immune functions were strongly affected, including temporally overlapping innate and adaptive immunity and macrophage M1 and M2 phenotype-related genes. The strong immune gene activation was accompanied by the sustained infiltration of peripheral immune cells at acute, subacute, and recovery stages of stroke. The infiltrated immune cells were found in the infarcted area but also in remote regions at 2 months after stroke. CONCLUSIONS: The study identifies that immune components are the predominant molecular signatures and they may propagate or continuously respond to brain injury in the subacute to chronic phase after central nervous system injury. The study suggests a potential immune-based strategy to modify injury progression and tissue remodeling in ischemic stroke, even months after the initiating event.


Assuntos
Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/imunologia , Movimento Celular/fisiologia , Imunidade Celular/fisiologia , Recuperação de Função Fisiológica/fisiologia , Transcrição Genética/fisiologia , Animais , Isquemia Encefálica/genética , Células Cultivadas , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL
16.
J Antimicrob Chemother ; 75(10): 2977-2980, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32607555

RESUMO

BACKGROUND: Remdesivir is a prodrug of the nucleoside analogue GS-441524 and is under evaluation for treatment of SARS-CoV-2-infected patients. OBJECTIVES: To evaluate the pharmacokinetics of remdesivir and GS-441524 in plasma, bronchoalveolar aspirate (BAS) and CSF in two critically ill COVID-19 patients. METHODS: Remdesivir was administered at 200 mg loading dose on the first day followed by 12 days of 100 mg in two critically ill patients. Blood samples were collected immediately after (C0) and at 1 (C1) and 24 h (C24) after intravenous administration on day 3 until day 9. BAS samples were collected on Days 4, 7 and 9 from both patients while one CSF on Day 7 was obtained in one patient. Remdesivir and GS-441524 concentrations were measured in these samples using a validated UHPLC-MS/MS method. RESULTS: We observed higher concentrations of remdesivir at C0 (6- to 7-fold higher than EC50 from in vitro studies) and a notable decay at C1. GS-441524 plasma concentrations reached a peak at C1 and persisted until the next administration. Higher concentrations of GS-441524 were observed in the patient with mild renal dysfunction. Mean BAS/plasma concentration ratios of GS-441524 were 2.3% and 6.4% in Patient 1 and Patient 2, respectively. The CSF concentration found in Patient 2 was 25.7% with respect to plasma. GS-441524 levels in lung and CNS suggest compartmental differences in drug exposure. CONCLUSIONS: We report the first pharmacokinetic evaluation of remdesivir and GS-441524 in recovered COVID-19 patients. Further study of the pharmacokinetic profile of remdesivir, GS-441524 and the intracellular triphosphate form are required.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Trifosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/farmacocinética , Betacoronavirus , Infecções por Coronavirus/metabolismo , Estado Terminal/terapia , Pneumonia Viral/metabolismo , Monofosfato de Adenosina/farmacocinética , Monofosfato de Adenosina/uso terapêutico , Trifosfato de Adenosina/farmacocinética , Trifosfato de Adenosina/uso terapêutico , Idoso , Alanina/farmacocinética , Alanina/uso terapêutico , Antivirais/uso terapêutico , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Feminino , Humanos , Masculino , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/tratamento farmacológico , Recuperação de Função Fisiológica/efeitos dos fármacos , Recuperação de Função Fisiológica/fisiologia
17.
Neurology ; 95(10): e1362-e1371, 2020 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-32641533

RESUMO

OBJECTIVE: To evaluate whether the relationship between systolic blood pressure (SBP) and stroke outcome varies during the acute stage of ischemic stroke as a function of the elapsed time after stroke onset. METHODS: Patients who were hospitalized due to ischemic stroke within 6 hours of onset were retrospectively analyzed. SBP data were collected at 8 time points (1, 2, 4, 8, 16, 24, 48, and 72 hours after onset). The primary functional outcome measure was a poor outcome, defined as a modified Rankin Scale score of >2 at 3 months after stroke. Linear and quadratic models were constructed at each time point to assess relationships between SBP and outcome. RESULTS: Of the 2,546 patients, 728 (28.6%) had a poor outcome. SBP, as either a linear or quadratic term, had a significant effect on functional outcome, except at 4 hours after onset. For the initial 2 hours after onset, SBP had nonlinear U-shaped relationships with functional outcome, and patients with SBP of approximately 165 mm Hg were the least likely to have a poor outcome. Quadratic models exhibited a significantly better model fit. For 8-24 hours postonset, SBP exhibited linear relationships with functional outcome. For 48-72 hours postonset, SBP exhibited a J-shaped relationship with functional outcome, and the predicted probability of poor outcome was the lowest in patients with SBP of approximately 125 mm Hg. These relationships were relatively consistent across various sensitivity analyses. CONCLUSION: This study revealed that the relationship between SBP and functional outcome may depend on elapsed time from stroke onset.


Assuntos
Pressão Sanguínea/fisiologia , Hipertensão/fisiopatologia , Recuperação de Função Fisiológica/fisiologia , Acidente Vascular Cerebral/fisiopatologia , Idoso , Isquemia Encefálica/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Acidente Vascular Cerebral/etiologia , Fatores de Tempo
18.
Am J Ophthalmol ; 218: 247-254, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32533947

RESUMO

PURPOSE: To investigate the association between optical coherence tomography (OCT) parameters and long-term visual recovery following optic chiasm decompression surgery. DESIGN: Prospective cohort study. METHODS: Consecutive patients who underwent pituitary or parasellar tumor resection between January 2009 to December 2018 were recruited in a single-center, 2-year prospective, longitudinal cohort study. Best-corrected visual acuity, visual fields, and OCT retinal nerve fiber layer (RNFL) thickness, macular thickness and volume were assessed preoperatively, and at 6 weeks, 6 months, and 2 years postoperatively. Long-term visual field recovery and maintenance were defined as a mean deviation of >-3 at 24 months, and visual acuity recovery and maintenance were defined as a logarithm of minimal angle of resolution (logMAR) of 0 (Snellen 20/20) or better at 24 months. RESULTS: A total of 239 patients (129 men, 110 women; mean ± SD age: 52 ± 16 years) were included. Multiple logistic regression analysis demonstrated that increased inferior RNFL thickness (per 10 µm) was associated with higher odds of long-term visual field recovery and maintenance (odds ratio [OR]: 1.26; 95% confidence interval [CI]: 1.12-1.41; Q < 0.001), and greater superior RNFL thickness (per 10 µm) was associated with higher odds of visual acuity recovery and maintenance (OR: 1.13; 95% CI: 1.03-1.27; Q = 0.031). A multivariable risk prediction model developed for long-term visual field recovery and maintenance that incorporated age, preoperative visual function, and RNFL thickness demonstrated C-statistics of 0.83 (95% CI: 0.72-0.94). CONCLUSION: Preoperative RNFL thickness was associated with long-term visual recovery and maintenance following chiasmal decompression. The multivariable risk prediction model developed in the present study may assist with preoperative patient counseling and prognosis.


Assuntos
Neoplasias Hipofisárias/cirurgia , Recuperação de Função Fisiológica/fisiologia , Acuidade Visual/fisiologia , Campos Visuais/fisiologia , Adulto , Idoso , Descompressão Cirúrgica , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fibras Nervosas/patologia , Quiasma Óptico/patologia , Quiasma Óptico/cirurgia , Neoplasias Hipofisárias/patologia , Prognóstico , Estudos Prospectivos , Células Ganglionares da Retina/patologia , Tomografia de Coerência Óptica
19.
PLoS One ; 15(6): e0235149, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32574215

RESUMO

Despite the multitude of adverse physical and psychosocial consequences of sports injury, evidence also highlights the potential for positive benefits in the injury aftermath. The purpose of this study is to address this gap by exploring the dimensions of personal growth following a severe sports injury. A 3-rounds e-Delphi method was utilized to develop a consensual understanding of the dimensions of sport-injury related growth. A panel of 24 psychology of sport injury experts participated in the process. The final list of items obtained was subjected to conventional content analysis to identify general themes. The process led to the development of a 5-dimension model capable of describing athletes' experiences of personal growth following a severe sports-related injury: personal strength, improved social life, health benefits, sport benefits, and social support and recognition. The domains of sport-injury related growth identified here are consistent with growth-domains identified in previous personal growth literature. However, they also highlight the importance of contextualizing the experience of growth. We have captured key elements of sport-injury related growth, domains that can be used as the basis for further psychometric testing and for further interventions to increase adjustment and well-being during the rehabilitation process.


Assuntos
Atletas/psicologia , Traumatismos em Atletas/psicologia , Técnica Delfos , Medicina Esportiva/métodos , Esportes/psicologia , Adaptação Psicológica/fisiologia , Traumatismos em Atletas/fisiopatologia , Traumatismos em Atletas/reabilitação , Humanos , Psicologia do Esporte/métodos , Psicologia do Esporte/estatística & dados numéricos , Recuperação de Função Fisiológica/fisiologia , Habilidades Sociais , Esportes/fisiologia , Inquéritos e Questionários
20.
J Rehabil Med ; 52(6): jrm00071, 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32488283

RESUMO

OBJECTIVE: To compare to what extent the presence of contralateral spatial neglect affects functional recovery and outcome among patients with right or left stroke after subacute inpatient rehabilitation. METHODS: Observational cohort study comparing functional improvement and outcome. The same admission data-set was used as in part 1 of this study. RESULTS: Right and left stroke rehabilitants with equally mild neglect and those without neglect (a total of 4 subgroups) all improved proportionally as much, but those with neglect, irrespective of stroke side needed a longer stay in inpatient rehabilitation. At discharge, total disability did not differ significantly between the 2 neglect subgroups, but those with left stroke had significantly lower Functional Independence Measure cognitive sub-score and score in communication. Rehabilitants with neglect, irrespective of stroke side had higher motor, cognitive and total disability and were more often institutionalized than those without neglect. CONCLUSION: Mild neglect did not impair recovery after right or left stroke, but rehabilitants with neglect were more disabled and needed a longer rehabilitation inpatient stay than those without neglect.


Assuntos
Recuperação de Função Fisiológica/fisiologia , Reabilitação do Acidente Vascular Cerebral/métodos , Acidente Vascular Cerebral/complicações , Estudos de Coortes , Avaliação da Deficiência , Feminino , Humanos , Pacientes Internados , Masculino , Alta do Paciente , Transtornos da Percepção/reabilitação , Acidente Vascular Cerebral/patologia
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