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1.
Mol Neurobiol ; 59(4): 2389-2406, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35084654

RESUMO

Focal cortical dysplasia (FCD) is associated with blood-brain barrier (BBB) dysfunction in patients with difficult-to-treat epilepsy. However, the underlying cellular and molecular factors in cortical dysplasia (CD) associated with progressive neurovascular challenges during the pro-epileptic phase, post-seizure, and during epileptogenesis remain unclear. We studied the BBB function in a rat model of congenital (in utero radiation-induced, first hit) CD and longitudinally examined the cortical brain tissues at baseline and the progressive neurovascular alterations, glucose transporter-1 (GLUT1) expression, and glucose metabolic activity at 2, 15, and 30 days following a second hit using pentylenetetrazole-induced seizure. Our study revealed through immunoblotting, immunohistochemistry, and biochemical analysis that (1) altered vascular density and prolongation of BBB albumin leakages in CD rats continued through 30 days post-seizure; (2) CD brain tissues showed elevated matrix metalloproteinase-9 levels at 2 days post-seizure and microglial overactivation through 30 days post-seizure; (3) BBB tight junction protein and GLUT1 levels were decreased and neuronal monocarboxylate transporter-2 (MCT2) and mammalian target of rapamycin (mTOR) levels were increased in the CD rat brain: (4) ATPase activity is elevated and a low glucose/high lactate imbalance exists in CD rats; and (5) the mTOR pathway is activated and MCT2 levels are elevated in the presence of high lactate during glucose starvation in vitro. Together, this study suggests that BBB dysfunction, including decreased GLUT1 expression and metabolic disturbance, may contribute to epileptogenesis in this CD rat model through multiple mechanisms that could be translated to FCD therapy in medically refractory epilepsy.


Assuntos
Epilepsia , Malformações do Desenvolvimento Cortical , Animais , Barreira Hematoencefálica/metabolismo , Glucose/metabolismo , Transportador de Glucose Tipo 1/metabolismo , Ácido Láctico , Mamíferos/metabolismo , Ratos , Convulsões , Serina-Treonina Quinases TOR/metabolismo
2.
Adv Neonatal Care ; 21(6): 503-512, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33783384

RESUMO

BACKGROUND: Failure of the car seat tolerance screen (CSTS) during hospitalization often leads to a recommendation for automobile travel within a car bed at discharge. PURPOSE: To describe the parental experience utilizing a car bed for infant automobile transportation. METHODS: A descriptive, qualitative study design was undertaken with a purposive sample of parents recruited for a single interview in the pulmonary clinic at the time of the follow-up CSTS, approximately 1 month after hospital discharge. Interviews, guided by a semistructured interview tool, provided a holistic understanding of the parental experience utilizing car bed travel. FINDINGS/RESULTS: Data from 15 parental interviews revealed an overarching emotional journey consisting of 5 themes: (1) an adjustment period; (2) decision-making related to the car bed purchase; (3) encounters with varied provider education and knowledge; (4) safety and security of the car bed during transit; and (5) space and mobility restrictions imposed by the car bed. IMPLICATIONS FOR PRACTICE: While recommendations exist for infant travel in a car seat, supportive recommendations for parents with an infant who needs to travel in a car bed do not exist. Based on study findings, providing parents supportive guidelines, education, and recommendations for their infant requiring travel in a car bed may be a strategy to ease the stress experienced in this situation. IMPLICATIONS FOR RESEARCH: Findings indicated a need to develop policies and standards, as well as comprehensive education, for providers and parents related to car bed travel. Further research is needed to identify strategies to best support parents and infants.


Assuntos
Sistemas de Proteção para Crianças , Equipamentos para Lactente , Apneia , Automóveis , Humanos , Lactente , Recém-Nascido , Pais
3.
J Affect Disord ; 148(1): 141-5, 2013 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-23219061

RESUMO

INTRODUCTION: A pilot trial was carried out to determine if a focussed narrative interview could alleviate the components of suffering and anxiety and depression in advanced cancer patients. INTERVENTION: Patients recruited were invited to participate in a focussed narrative interview and reflect on their perspectives on their sense of "meaning", regarding suffering and their psychological, physical, social and spiritual well being - the emphasis was on allowing the patient to tell their story. Patients were encouraged to share what resources they themselves had utilised in addition to what professional care they may have received, to maintain a sense of well being. METHOD: Patients with advanced metastatic disease were recruited from hospices in the North West of England - the only exclusion criteria were not being able to understand written and spoken English and a non cancer diagnosis. At recruitment patients were asked to complete a numerical scale for suffering; the Brief Edinburgh Depression Scale, Edmonton Symptom Assessment Scale (ESAS), FACIT Spiritual well being questionnaire, Demographic information was collected and patients were randomised to either the intervention arm of the trial or the usual care arm of the study. Patients in both groups were invited to complete each measure at 2, 4 and 8 weeks. RESULTS: One hundred people were recruited into the study - 49 were randomised to intervention group and 51 to control group. The median age of patients was 66 years age range (31-89 years) and 68% of patients were female. At baseline the ECOG performance of 75% of patients recruited was 1 or 2. The median survival of all patients in the study was 169.5 days (range 10 days to still alive at end of study). There was no significant difference at any timepoint in scores on suffering measure between intervention group and control group. At each time point the intervention demonstrated mean improvement in scores for depression and anxiety on ESAS - the greatest changes for both depression and anxiety were seen at 4 weeks. CONCLUSION: This pilot randomised controlled trial of a focussed narrative intervention demonstrated an improvement in mean changes in scores for depression and anxiety at 2, 4, and 8 weeks. We suggest this intervention may have beneficial effects on depression and anxiety, but a larger powered trial is required to determine the full effects.


Assuntos
Ansiedade/prevenção & controle , Depressão/prevenção & controle , Neoplasias/psicologia , Psicoterapia/métodos , Estresse Psicológico/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Inglaterra , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Narração , Estadiamento de Neoplasias , Neoplasias/patologia , Projetos Piloto , Resultado do Tratamento
4.
Int J MS Care ; 14(2): 65-70, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-24453736

RESUMO

The ability to drive is often affected in individuals with multiple sclerosis (MS) because of the motor, visual, or cognitive deficits commonly associated with the condition. In this study, we investigated the accuracy with which the Stroke Driver Screening Assessment (SDSA), an established battery for the prediction of driving performance of stroke survivors, would predict driving performance of individuals with MS. Driving performance of 44 individuals with relapsing-remitting MS (mean ± SD age, 46 ± 11 years; 37 females and 7 males) who were currently driving at least once a month was predicted using their performance on the SDSA. Outcomes of a road test and the Useful Field of View (UFOV) test were used as measures of driving ability. Participants' performance on both the road and UFOV tests was predicted with more than 80% accuracy. The SDSA was more accurate in predicting who would pass the two tests than who would fail the tests. The SDSA battery appears to be a good predictor of driving performance of individuals with relapsing-remitting MS, especially those who have sufficient cognitive skills to continue driving. Larger studies are needed to definitively establish its predictive accuracy and confirm the validity of the predictions.

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