Coagulation Factor Binding Orientation and Dimerization May Influence Infectivity of Adenovirus-Coagulation Factor Complexes.

Coagulation factor binding orientation and dimerization may influence infectivity of adenovirus-coagulation factor complexes.

J Virol. 2013 Jun 26;
Irons EE, Flatt JW, Doronin K, Fox TL, Acchione M, Stewart PL, Shayakhmetov DM

Adenoviruses (Ads) are promising vectors for therapeutic interventions in humans. When injected into the bloodstream, Ad vectors can bind several vitamin K-dependent blood coagulation factors, which contribute to virus sequestration in the liver by facilitating transduction of hepatocytes. Although both coagulation factors FVII and FX bind hexon of human Ad serotype 5 (HAdv5) with very high affinity, only FX appears to play a role in mediating Ad hepatocyte transduction in vivo. To understand the discrepancy between efficacy of FVII binding to the hexon and its apparent poor capacity at supporting virus cell entry, we analyzed the HAdv5-FVII complex using high-resolution cryo-electron microscopy, followed by molecular dynamics flexible fitting (MDFF) simulations. The results indicate that although hexon amino acids T423-E424-T425 that were earlier identified as critical for FX binding are also involved in mediating binding of FVII, the FVII GLA-domain sits within the surface-exposed hexon trimer depression in a different orientation than found for FX. Furthermore, we found that when bound to the hexon, two proximal FVII molecules interact via their serine protease (SP) domains and bury potential heparan sulfate proteoglycan (HSPG) receptor binding residues within the dimer interface. In contrast, earlier cryo-EM studies of the Ad-FX interaction showed no evidence of dimer formation. Dimerization of FVII when bound to Ad may be a contributing mechanistic factor for the differential infectivity of Ad-FX and Ad-FVII complexes, despite high affinity binding of both of these coagulation factors to the virus. HubMed – depression

 

Impact of An Evidence Based Prenatal Care Model on Patient Outcomes.

J Prim Care Community Health. 2010 Oct 1; 1(3): 168-172
Lewallen LP, Jarrett-Pulliam C, Dixon KH

Health care providers face many challenges when providing prenatal care. This article reports on a program called Prenatal Care: the Beginning of a Lifetime (PCBL), to implement standardized prenatal care in central North Carolina. The purpose of this pilot study was to determine if there were differences in patient outcomes between a control group and 3 groups (A, B, and C) of increasing levels of intervention in standardized prenatal care. A total of 150 patients were enrolled and followed through delivery. There were no significant differences between the groups in cigarette smoking status, weight gain, genetic screening, sexually transmitted infection screening, diabetes screening, domestic violence assessment, 17P candidacy assessment, gestational age at delivery, or infant birth weight. However, a significant difference was found in depression screening. An association between intervention group membership and likelihood of being screened for depression was found in each trimester. As the level of intervention increased, the number of participants screened for depression increased significantly. HubMed – depression

 

Postpartum Depression Screening: Initial Implementation in a Multispecialty Practice With Collaborative Care Managers.

J Prim Care Community Health. 2010 Oct 1; 1(3): 158-163
Wichman CL, Angstman KB, Lynch B, Whalen D, Jacobson N

Postpartum depression (PPD) has emerged as an important issue for pediatricians and family practitioners because of detrimental effects on children. PPD occurs in 10% to 22% of women who have recently given birth, but fewer than half of cases are recognized. Despite the impact of PPD, many primary care clinicians do not have systemic screening approaches implemented. This paper will review the development of a screening protocol for PPD in a multispecialty clinic, with the implementation utilizing depression care managers and the preliminary results of our process. Of the 333 screened examinations during the 4-month study, 38.1% (n = 127) were performed for the 2-month well child examination; 33.6% (n = 112) were for the 4-month examination, with 28.2% (n = 94) being performed for the 6-month well child examination. Only 15 (4.5%) were positive for possible depression with a screening compliance rate of 47.9%. No significant difference was noted in the timing of the well child visit with a positive screening test result, nor was there any difference in family medicine versus pediatric colleagues in the utilization of the screening or diagnosis of PPD. Implementation of PPD screening in a multispecialty clinic can be effective, given utilization of depression care managers. HubMed – depression