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Eligibility Determination↗
Biomedical subjects
Stephen Burke
Publications and source records attributed to Stephen Burke.
Structural basis of West Nile virus neutralization by a therapeutic antibody.
West Nile virus is a mosquito-borne flavivirus closely related to the human epidemic-causing dengue, yellow fever and Japanese encephalitis viruses. In establishing infection these icosahedral viruses undergo endosomal membrane fusion catalysed by envelope glycoprotein rearrangement of the putative receptor-binding domain III (DIII) and exposure of the hydrophobic fusion loop. Humoral immunity has an essential protective function early in the course of West Nile virus infection. Here, we investigate the mechanism of neutralization by the E16 monoclonal antibody that specifically binds DIII. Structurally, the E16 antibody Fab fragment engages 16 residues positioned on four loops of DIII, a consensus neutralizing epitope sequence conserved in West Nile virus and distinct in other flaviviruses. The E16 epitope protrudes from the surface of mature virions in three distinct environments, and docking studies predict Fab binding will leave five-fold clustered epitopes exposed. We also show that E16 inhibits infection primarily at a step after viral attachment, potentially by blocking envelope glycoprotein conformational changes. Collectively, our results suggest that a vaccine strategy targeting the dominant DIII epitope may elicit safe and effective immune responses against flaviviral diseases.
Adsorption↗
Value children, value child care.
Evidence suggests that quality child care is good for children, good for parents and good for society, but there is a shortage of day-care places and not all parents who want one can afford it. The workforce who undertake the day care of young children deserve greater recognition for what they do and should be well trained and well rewarded.
Adult↗
Sagittal plane deformity in the thoracic spine: a clue to the presence of syringomyelia as a cause of scoliosis.
STUDY DESIGN: A retrospective review of scoliosis radiographs of 93 patients with either idiopathic scoliosis or syringomyelia-associated scoliosis were assessed, defining their sagittal alignment. OBJECTIVE: To validate an observation regarding the absence of Dickson's sagittal deformity of the thoracic spine in patients with syringomyelia-associated scoliosis. SUMMARY OF BACKGROUND DATA: Patients with adolescent idiopathic scoliosis have a classic sagittal deformity. Dickson described that patients with adolescent idiopathic scoliosis (AIS) have an associated lordotic deformity at the apex of their coronal deformity. MATERIALS AND METHODS: Retrospective reviews of standard scoliosis series radiographs of 93 patients with idiopathic or syringomyelia-associated scoliosis from two institutions were compared. Particular attention was given to the lateral radiograph of the spine assessing presence or absence of Dickson's apical lordosis. Nine patients had to be excluded because of inadequate imaging. The study group consisted of 30 patients with scoliosis from TSRH with documented syringomyelia identified between 1985 and 1997. The demographic and radiographic features of this group were compared with those of a control group consisting of a consecutive series of 54 patients from HSS with adolescent idiopathic and normal MRI. The groups were comparable for age (mean age: control 13 y; syrinx 12 y) and curve pattern but differed in curve magnitude (mean Cobb: control 50 degrees; syrinx 40 degrees ). RESULTS: Apical lordosis was present in 97% of patient with AIS and a normal MRI but was absent in 75% of patients with syringomyelia-associated scoliosis (P < 0.0001). The results also confirmed that male patients with scoliosis and left-side curves have a predisposition to having a syringomyelia (P < 0.0001). CONCLUSIONS: Sagittal plane deformity in scoliosis can be an indicator of the presence of a syringomyelia. Our results reinforce the necessity of assessing sagittal plane deformity when treating scoliosis. If apical lordotic deformity is absent, a diagnosis of idiopathic scoliosis should be made with caution.
Adolescent↗
Transthoracic US of the chest: clinical uses and applications.
Transthoracic ultrasound (US) of the chest is useful in the evaluation of a wide range of peripheral parenchymal, pleural, and chest wall diseases. Furthermore, it is increasingly used to guide interventional procedures of the chest and pleural space. The technique lends itself to bedside use in the intensive care unit, where suboptimal radiography may mask or mimic clinically significant abnormalities. The authors discuss the uses, techniques and applications of US of the chest. The sonographic appearances of pleural diseases (pleural effusion, pneumothorax, pleural mass, and mesothelioma), parenchymal diseases (pneumonia, neoplasms, heart failure, infarct, and rounded atelectasis), chest wall abnormalities (chest wall tumor and rib fracture), and diaphragmatic paralysis are discussed. The use of US in guiding biopsy, thoracocentesis, and other interventional procedures of the lung, pleural space, and mediastinum are also reviewed.
Biopsy↗