No abstract

Summary Adaptor proteins play a critical role in the assembly of signaling complexes after engagement of platelet receptors by agonists such as collagen, ADP and thrombin. Recently, using proteomics, the Dok (downstream of tyrosine kinase) adapter proteins were identified in human and mouse platelets. In vitro studies suggest that Dok-1 binds to platelet integrin β3, but the underlying effects of Dok-1 on αIIbβ3 signaling, platelet activation and thrombosis remain to be elucidated. In the present study, using Dok-1-deficient (Dok-1−/−) mice, we determined the phenotypic role of Dok-1 in αIIbβ3 signaling. We found that platelets from Dok-1−/− mice displayed normal aggregation, activation of αIIbβ3 (assessed by binding of JON/A), P-selectin surface expression (assessed by anti-CD62P), and soluble fibrinogen binding. These findings indicate that Dok-1 does not affect “inside-out” platelet signaling. Compared with platelets from wild-type (WT) mice, platelets from Dok-1−/− mice exhibited increased clot retraction (P < 0.05 vs WT), increased PLCγ2 phosphorylation, and enhanced spreading on fibrinogen after thrombin stimulation (P < 0.01 vs. WT), demonstrating that Dok-1 negatively regulates αIIbβ3 “outside-in” signaling. Finally, we found that Dok-1−/− mice exhibited significantly shortened bleeding times and accelerated carotid artery thrombosis in response to photochemical injury (P < 0.05 vs. WT mice). We conclude that Dok-1 modulates thrombosis and hemostasis by negatively regulating αIIbβ3 outside-in signaling.

The value of routine coagulation testing instead of bleeding history alone in children, to predict bleeding risk prior to tonsillectomy and adenoidectomy has been questioned. Our objectives are to identify the causes of abnormal PT and/or aPTT in these patients, and to determine whether routine preoperative coagulation testing is effective in identifying children with a clinically significant coagulation abnormality prior to undergoing a procedure. In this study, data were extracted by chart review for 854 patients referred to the pediatric hematology service at Stony Brook University for the evaluation of an elevated PT and/or aPTT on preoperative testing. Seven hundred and ninety two of 854 reviewed charts (92.7%) contained sufficient data for analysis. On repeat testing, 393 (49.6%) had a laboratory abnormality identified. A potentially significant coagulation abnormality was identified in 32 of 792 patients (4%). For the remaining 760 patients, the most common diagnosis was a lupus anticoagulant (n = 98, 24.6%) or a "presumed" lupus anticoagulant (n = 166, 41.6%). A positive personal or family bleeding history was documented in 268 patients (268/792 = 33.8%). Of these patients, only 107 (39.9%) had an abnormality identified on further work-up. Seventeen of the 32 patients with clinically significant bleeding disorders identified were found to have a positive bleeding history (17/32 = 53.1%). Routine preoperative coagulation testing identifies only a small number of children at increased risk for surgical bleeding. However, a "positive" bleeding history identifies only 60% of children found to have a clinically significant coagulation abnormality. Routine preoperative coagulation testing may serve as a useful adjunct to clinical history.

Objective:The objective of this study is to assess the prevalence of sleep disorders among children aging between 4 and 9 years using Hindi version of Pediatric Sleep Questionnaire (PSQ).Methods:This study had two parts first, translation and validation of PSQ into Hindi language, and second, assessment of the prevalence of sleep disorders using PSQ Hindi version. Hindi PSQ was distributed in randomly chosen primary schools in a semi-urban area. The children were requested to get them filled by their parents. When the questionnaires were returned, responses were analyzed.Results:Most of the items of the Hindi version had perfect agreement with original questionnaire in a bilingual population (κ =1). Totally, 435 children were included in the field study having average age of 6.3 years. Obstructive sleep apnea was reported in 7.5% children; symptoms suggestive of restless legs syndrome were reported by 2%–3%; teeth grinding by 13.9% and sleep talking by 22.6% children.Conclusion:PSQ Hindi version is a validated tool to screen for sleep disorders among children. Sleep disorders are fairly prevalent among young children in India.

Transcutaneous electrical nerve stimulation therapy was effective for stimulation of whole saliva in normal, healthy subjects and its effect retained till 30 minutes and a little up to 24 hours. Transcutaneous electrical nerve stimulation may work best synergistically with other sialagogues and can be used for the management of xerostomia.