Delivering Challenging News: An Illness-Trajectory Communication Curriculum for Multispecialty Oncology Residents and Fellows

Introduction: Published curricula to teach communication skills for postgraduate fellows in oncology are few in number despite the fact that oncologists conduct many difficult discussions with their patients and their families. Such discussions may include disclosing initial diagnosis or relapse of a patient\u27s cancer or relaying a poor prognosis or change to palliative care. Methods: An eight-module course on communication in oncology practice was delivered over 2 months for palliative and oncology fellows and radiation oncology residents. Learners were given a precourse survey in which they were asked to rate their proficiency in various communication tasks. Each learner then participated in a videotaped precourse objective structured clinical exam (OSCE) on breaking bad news with standardized patients (SPs). The course took place over 8 weeks with weekly didactics and role-play. At the end of the course, a second OSCE took place. After the course was completed, the fellows again filled out a proficiency survey. Results: Twenty-two learners participated over 2 years of this course. Participants reported a significant increase in perceived competence in all areas on the postcourse survey. SP feedback on OSCEs pre- and postcourse indicated improvement in skills for learners. Pre- and postcourse OSCE video assessment revealed a significant improvement in global communication skills. Discussion: Initial data show that this course successfully improved communication skills and increased fellows\u27 comfort level across several domains of communication. Future directions include validating our assessment tool, expanding the topic base, and investigating the impact on practice after course completion

Measuring cognitive load: mixed results from a handover simulation for medical students.

The application of cognitive load theory to workplace-based activities such as patient handovers is hindered by the absence of a measure of the different load types. This exploratory study tests a method for measuring cognitive load during handovers.The authors developed the Cognitive Load Inventory for Handoffs (CLI4H) with items for intrinsic, extraneous, and germane load. Medical students completed the measure after participating in a simulated handover. Exploratory factor and correlation analyses were performed to collect evidence for validity.Results yielded a two-factor solution for intrinsic and germane load that explained 50 % of the variance. The extraneous load items performed poorly and were removed from the model. The score for intrinsic load correlated with the Paas Cognitive Load scale (r = 0.31, p = 0.004) and was lower for students with more prior handover training (p = 0.036). Intrinsic load did not, however, correlate with performance. Germane load did not correlate with the Paas Cognitive Load scale but did correlate as expected with performance (r = 0.30, p = 0.005) and was lower for those students with more prior handover training (p = 0.03).The CLI4H yielded mixed results with some evidence for validity of the score from the intrinsic load items. The extraneous load items performed poorly and the use of only a single item for germane load limits conclusions. The instrument requires further development and testing. Study results and limitations provide guidance to future efforts to measure cognitive load during workplace-based activities, such as handovers

Antagonism of the complement component C4 by flavivirus nonstructural protein NS1

The complement system plays an essential protective role in the initial defense against many microorganisms. Flavivirus NS1 is a secreted nonstructural glycoprotein that accumulates in blood, is displayed on the surface of infected cells, and has been hypothesized to have immune evasion functions. Herein, we demonstrate that dengue virus (DENV), West Nile virus (WNV), and yellow fever virus (YFV) NS1 attenuate classical and lectin pathway activation by directly interacting with C4. Binding of NS1 to C4 reduced C4b deposition and C3 convertase (C4b2a) activity. Although NS1 bound C4b, it lacked intrinsic cofactor activity to degrade C4b, and did not block C3 convertase formation or accelerate decay of the C3 and C5 convertases. Instead, NS1 enhanced C4 cleavage by recruiting and activating the complement-specific protease C1s. By binding C1s and C4 in a complex, NS1 promotes efficient degradation of C4 to C4b. Through this mechanism, NS1 protects DENV from complement-dependent neutralization in solution. These studies define a novel immune evasion mechanism for restricting complement control of microbial infection

Recombinant human complement component C2 produced in a human cell line restores the classical complement pathway activity in-vitro: an alternative treatment for C2 deficiency diseases

Background: Complement C2 deficiency is the most common genetically determined complete complement deficiency and is associated with a number of diseases. Most prominent are the associations with recurrent serious infections in young children and the development of systemic lupus erythematosus (SLE) in adults. The links with these diseases reflect the important role complement C2 plays in both innate immunity and immune tolerance. Infusions with normal fresh frozen plasma for the treatment of associated disease have demonstrated therapeutic effects but so far protein replacement therapy has not been evaluated. Results: Human complement C2 was cloned and expressed in a mammalian cell line. The purity of recombinant human C2 (rhC2) was greater than 95% and it was characterized for stability and activity. It was sensitive to C1s cleavage and restored classical complement pathway activity in C2-deficient serum both in a complement activation ELISA and a hemolytic assay. Furthermore, rhC2 could increase C3 fragment deposition on the human pathogen Streptococcus pneumoniae in C2-deficient serum to levels equal to those with normal serum. Conclusions: Taken together these data suggest that recombinant human C2 can restore classical complement pathway activity and may serve as a potential therapeutic for recurring bacterial infections or SLE in C2-deficient patients

The structure of the tetrasialoganglioside from human brain

Autosomal dominant retinal vasculopathy with cerebral leukodystrophy is a microvascular endotheliopathy with middle- age onset. In nine families, we identified heterozygous C- terminal frameshift mutations in TREX1, which encodes a 3'-5' exonuclease. These truncated proteins retain exonuclease activity but lose normal perinuclear localization. These data have implications for the maintenance of vascular integrity in the degenerative cerebral microangiopathies leading to stroke and dementias