Publications

Deep sequencing was used to discover a novel rhabdovirus (Bas-Congo virus, or BASV) associated with a 2009 outbreak of 3 human cases of acute hemorrhagic fever in Mangala village, Democratic Republic of Congo (DRC), Africa. The cases, presenting over a 3-week period, were characterized by abrupt disease onset, high fever, mucosal hemorrhage, and, in two patients, death within 3 days. BASV was detected in an acute serum sample from the lone survivor at a concentration of 1.09 × 10(6) RNA copies/mL, and 98.2% of the genome was subsequently de novo assembled from ≈ 140 million sequence reads. Phylogenetic analysis revealed that BASV is highly divergent and shares less than 34% amino acid identity with any other rhabdovirus. High convalescent neutralizing antibody titers of >1:1000 were detected in the survivor and an asymptomatic nurse directly caring for him, both of whom were health care workers, suggesting the potential for human-to-human transmission of BASV. The natural animal reservoir host or arthropod vector and precise mode of transmission for the virus remain unclear. BASV is an emerging human pathogen associated with acute hemorrhagic fever in Africa.

Systemic antagonists of the histamine type 1 and 2 receptors (H1/2r) are widely used as anti-pruritics and central sedatives, but demonstrate only modest anti-inflammatory activity. Because many inflammatory dermatoses result from defects in cutaneous barrier function, and because keratinocytes express both Hr1 and Hr2, we hypothesized that H1/2r antagonists might be more effective if they were used topically to treat inflammatory dermatoses. Topical H1/2r antagonists additively enhanced permeability barrier homeostasis in normal mouse skin by the following mechanisms: (i) stimulation of epidermal differentiation, leading to thickened cornified envelopes; and (ii) enhanced epidermal lipid synthesis and secretion. As barrier homeostasis was enhanced to a comparable extent in mast cell-deficient mice, with no further improvement following application of topical H1/2r antagonists, H1/2r antagonists likely oppose mast cell-derived histamines. In four immunologically diverse, murine disease models, characterized by either inflammation alone (acute irritant contact dermatitis, acute allergic contact dermatitis) or by prominent barrier abnormalities (subacute allergic contact dermatitis, atopic dermatitis), topical H1/2r agonists aggravated, whereas H1/2r antagonists improved, inflammation and/or barrier function. The apparent ability of topical H1r/2r antagonists to target epidermal H1/2r could translate into increased efficacy in the treatment of inflammatory dermatoses, likely due to decreased inflammation and enhanced barrier function. These results could shift current paradigms of antihistamine utilization from a predominantly systemic to a topical approach.

BACKGROUND

Early recognition and management of chronic kidney disease (CKD) are associated with better outcomes. Internal medicine residency should prepare physicians to diagnose and manage CKD.

METHODS

To examine whether residency training and program characteristics were associated with CKD knowledge and investigate the effectiveness of an internet-based training module in improving CKD knowledge, we analyzed data from CKD training modules administered annually to U.S. internal medicine residents from July 1, 2005 to June 30, 2009. Baseline CKD knowledge was assessed using pre-tests. The modules' effectiveness was evaluated by post-tests. Comparisons were performed using X² tests and paired t-tests.

RESULTS

Of 4,702 residents, 38%, 33%, and 29% were program year (PGY)-1, PGY-2, and PGY-3, respectively. Baseline CKD knowledge was poor, with mean pre-test scores of 45.1-57.0% across the four years. The lowest pre-test performance was on CKD recognition. Pre-test scores were better with higher training levels (P-trend < 0.001 except 2005-2006 [P-trend = 0.35]). Affiliation with a renal fellowship program or program location within a region of high end-stage kidney disease prevalence was not associated with better baseline CKD knowledge. Completion of the CKD module led to significant improvements from pre- to post-test scores (mean improvement 27.8% [SD: 21.3%] which were consistent from 2005 to 2009.

CONCLUSIONS

Knowledge of diagnosis and management of CKD improves during residency training but remains poor among graduating residents. Web-based training can be effective in educating physicians on CKD-related issues. Studies are needed to determine whether knowledge gained from such an intervention translates to improved care of CKD patients.