Role of the B domain for factor VIII and factor V expression and function

Factor V and factor VIII are homologous cofactors in the blood coagulation cascade that have the domain structure A1-A2-B-A3-C1-C2, of which the B domain has extensively diverged. In transfected COS-1 monkey cells, expression of factor VIII is approximately 10-fold less efficient than that of factor V, primarily because of inefficient protein secretion and, to a lesser extent, reduced mRNA expression. To study the functional significance and effect of the B domain on expression and activity, chimeric cDNAs were constructed in which the B domains of factor V and factor VIII were exchanged. Expression of a factor VIII chimera harboring the B-domain of factor V yielded a fully functional factor VIII molecule that was expressed twofold more efficiently than wild-type factor VIII because of increased mRNA expression. Thus, sequences within the factor VIII B domain were not responsible for the inefficient secretion of factor VIII compared with factor V. Expression of a factor V chimera harboring the B domain of factor VIII was slightly reduced compared with wild-type factor V, although the secreted molecule had significantly reduced procoagulant activity correlating with dissociated heavy and light chains and resistance to thrombin activation. Interestingly, the factor V chimera containing the factor VIII B domain was efficiently activated by Russell's viper venum (RVV). A factor V B domain deletion (residues 710- 1545) molecule also exhibited significantly reduced procoagulant activity caused by resistance to thrombin cleavage and activation, although this molecule was activatable by RVV. These results show that, in contrast to factor VIII, thrombin activation of factor V requires sequences within the B domain. In addition, thrombin activation of factor V occurs through a different mechanism than activation by RVV.     

Opportunities to Improve Long COVID Care: Implications from Semi-structured Interviews with Black Patients

The Patient - Patient-Centered Outcomes Research - Long coronavirus disease (COVID) is an emerging condition that could considerably burden healthcare systems. Prior qualitative studies...     

Support interventions for caregivers of physically disabled adults: A systematic review

In developing countries family caregivers are an important community‐based resource who provide care for physically disabled adults. Substantial caregiving commitment is known to adversely affect caregiver health and thereby their capacity to provide ongoing care. This systematic review focused on support interventions for caregivers using Thailand as an example. From 1964 to 2011 international and Thai electronic databases and relevant grey literature were searched. Six English papers and 34 Thai papers published between 1990 and 2010 were found. The Critical Appraisal Skills Programme (CASP) tool was modified to appraise methodological quality. All nurse‐led interventions mainly focused on improving caregiving capacity; nearly half considered caregiver health. Only 15 interventions were community‐based. Despite variable research quality all studies showed benefits for caregivers, care recipients, and healthcare services. In developing countries without healthy caregivers physically disabled adults would not receive care. There is an urgent need for further investment in community‐based research to develop effective interventions designed to promote caregiver health and help them maintain their role.     

Duodenal hematoma: the ring sign in MR imaging

Proper management of duodenal hematoma requires that an accurate diagnosis be made using noninvasive radiological methods. Conventional imaging may be nonspecific if there is no history of trauma or coagulopathy. Two cases of duodenal hematoma that were imaged by magnetic resonance (MR) and computed tomography (CT) are described. In both cases the hematoma had a well-defined concentric ring configuration on MR images, a finding which helped establish the diagnosis. MR imaging may provide tissue-specific characterization of duodenal hematomas.     

Ferrite particles for bowel contrast in MR imaging: design issues and feasibility studies

Diverse materials with varying physical and magnetic properties have been evaluated as gastrointestinal contrast agents for magnetic resonance (MR) imaging. Uniform marking of the small bowel remains the greatest challenge. Ferrites are magnetically active iron oxide particles that are miscible with water and cause loss of signal on MR images. The decrease in MR signal intensity produced by ferrites occurs with a wide range of iron concentrations (0.1-10 mM) and with both T1- and T2-weighted pulse sequences. These effects of ferrites are explained by predominant T2 shortening with negligible T1 effects. The ferrite preparation used in this study was stable in vitro, with little iron solubilized by acid. Intragastric administration of ferrite (5 mg of iron per kg in 6 ml) routinely marked the small bowel of rats. The authors conclude that ferrites represent a promising new class of contrast agents for gastrointestinal MR imaging.     

Comparison of weekly and daily incremental protocols of narrowband ultraviolet B phototherapy for psoriasis

BACKGROUND: Different protocols have been used for narrowband ultraviolet B (UVB) therapy, commonly used in the treatment of psoriasis; however, more effective and reliable protocols are still required. OBJECTIVE: The aim of this study was to compare the weekly and daily dose increment protocols of narrowband UVB phototherapy in psoriasis patients. METHODS: Thirty patients with plaque psoriasis underwent narrowband UVB treatment three times a week and 15 patients selected consecutively among these patients underwent a weekly (once in three treatments) dose increment whereas the remaining 15 patients underwent a daily dose increment. Patients were monitored for 10 weeks and evaluated by the Psoriasis Area Severity Index (PASI). RESULTS: When the two groups were evaluated according to median PASI scores prior to the treatment and during 10 weeks of treatment, there was no statistically significant difference between the groups (P > 0.05). During the treatment lasting for 10 weeks, four patients in the group with a weekly dose increment and three patients in the group with a daily dose increment recovered and no statistically significant difference was detected between the groups (P > 0.05). The groups were also evaluated according to the median cumulative dose. The median cumulative dose was higher in the group with a daily dose increment and the difference between the groups was statistically significant (P = 0.002). CONCLUSION: The application of daily dose increments was no better than that of weekly dose increments in narrowband UVB treatment for psoriasis. Therefore, although our results may need to be supported by large-series studies, we conclude that application of weekly dose increments with a lower cumulative dose having the same efficacy is preferred in narrowband UVB treatment of psoriasis.