Publications

BACKGROUND

The Accreditation Council for Graduate Medical Education (ACGME) has established the requirement for residency programs to assess trainees' competencies in 6 core domains (patient care, medical knowledge, practice-based learning, interpersonal skills, professionalism, and systems-based practice). As attending rounds serve as a primary means for educating trainees at academic medical centers, our study aimed to identify current rounding practices and attending physician perceived capacity of different rounding models to promote teaching within the ACGME core competencies.

METHODS

We disseminated a 24-question survey electronically using educational and hospital medicine leadership mailing lists. We assessed attending physician demographics and the frequency with which they used various rounding models, as defined by the location of the discussion of the patient and care plan: bedside rounds (BR), hallway rounds (HR), and card-flipping rounds (CFR). Using the ACGME framework, we assessed the perceived educational value of each model.

RESULTS

We received 153 completed surveys from attending physicians representing 34 institutions. HR was used most frequently for both new and established patients (61% and 43%), followed by CFR for established patients (36%) and BR for new patients (22%). Most attending physicians indicated that BR and HR were superior to CFR in promoting the following ACGME competencies: patient care, systems-based practice, professionalism, and interpersonal skills.

CONCLUSIONS

HR is the most commonly employed rounding model. BR and HR are perceived to be valuable for teaching patient care, systems-based practice, professionalism, and interpersonal skills. CFR remains prevalent despite its perceived inferiority in promoting teaching across most of the ACGME core competencies.

OBJECTIVES

To determine the frequency and predictors of hypertension linkage to care after implementation of a linkage intervention in rural Uganda.

METHODS

During a multidisease screening campaign for HIV, diabetes and hypertension in rural Uganda, hypertensive adults received education, appointment to a local health facility and travel voucher. We measured frequency and predictors of linkage to care, defined as visiting any health facility for hypertension management within 6 months. Predictors of linkage to care were calculated using collaborative-targeted maximum likelihood estimation (C-TMLE). Participants not linking were interviewed using a standardised instrument to determine barriers to care.

RESULTS

Over 5 days, 2252 adults were screened for hypertension and 214 hypertensive adults received a linkage intervention for further management. Of these, 178 (83%) linked to care within 6 months (median = 22 days). Independent predictors of successful linkage included older age, female gender, higher education, manual employment, tobacco use, alcohol consumption, hypertension family history and referral to local vs. regional health centre. Barriers for patients who did not see care included expensive transport (59%) and feeling well (59%).

CONCLUSIONS

A community health campaign that offered hypertension screening, education, referral appointment and travel voucher achieved excellent linkage to care (83%). Young adults, men and persons with low levels of formal education were among those least likely to seek care.

Hepatic endoplasmic reticulum (ER) integral cytochromes P450 (P450s) are monooxygenases engaged in the biotransformation and elimination of endo- as well as xenobiotics. Of the human liver P450s, CYP3A4 is the major and most dominant catalyst responsible for the biotransformation of over 50% of clinically prescribed drugs. CYP2E1 metabolizes smaller molecular weight compounds (EtOH), carcinogens, environmental toxins, and endobiotics, and is justly implicated in various toxigenic/pathogenic mechanisms of human disease. Both P450s are notorious for their potential to generate pathogenic reactive oxygen species (ROS) during futile oxidative cycling and/or oxidative uncoupling. Such ROS not only oxidatively damage the P450 catalytic cage, but on their escape into the cytosol, also the P450 outer surface and any surrounding cell organelles. Given their ER-monotopic topology coupled with this high potential to acquire oxidative lesions in their cytosolic (C) domain, not surprisingly these P450 proteins exhibit shorter lifespans and are excellent prototype substrates of ER-associated degradation ("ERAD-C") pathway. Indeed, we have shown that both CYP3A4 and CYP2E1 incur ERAD-C, during which they are first phosphorylated by protein kinases A and C, which greatly enhance/accelerate their ubiquitination by UBC7/gp78 and UbcH5a/CHIP/Hsp70/Hsp40 E2/E3 ubiquitin ligase complexes. Such P450 phosphorylation occurs on Ser/Thr residues within linear sequences as well as spatially clustered acidic (Asp/Glu) residues. We propose that such S/T phosphorylation within these clusters creates negatively charged patches or conformational phosphodegrons for interaction with positively charged E2/E3 domains. Such P450 S/T phosphorylation we posit serves as a molecular switch to turn on its ubiquitination and ERAD-C.

BACKGROUND

Bronchial airway expression profiling has identified inflammatory subphenotypes of asthma, but the invasiveness of this technique has limited its application to childhood asthma.

OBJECTIVES

We sought to determine whether the nasal transcriptome can proxy expression changes in the lung airway transcriptome in asthmatic patients. We also sought to determine whether the nasal transcriptome can distinguish subphenotypes of asthma.

METHODS

Whole-transcriptome RNA sequencing was performed on nasal airway brushings from 10 control subjects and 10 asthmatic subjects, which were compared with established bronchial and small-airway transcriptomes. Targeted RNA sequencing nasal expression analysis was used to profile 105 genes in 50 asthmatic subjects and 50 control subjects for differential expression and clustering analyses.

RESULTS

We found 90.2% overlap in expressed genes and strong correlation in gene expression (ρ = .87) between the nasal and bronchial transcriptomes. Previously observed asthmatic bronchial differential expression was strongly correlated with asthmatic nasal differential expression (ρ = 0.77, P = 5.6 × 10(-9)). Clustering analysis identified TH2-high and TH2-low subjects differentiated by expression of 70 genes, including IL13, IL5, periostin (POSTN), calcium-activated chloride channel regulator 1 (CLCA1), and serpin peptidase inhibitor, clade B (SERPINB2). TH2-high subjects were more likely to have atopy (odds ratio, 10.3; P = 3.5 × 10(-6)), atopic asthma (odds ratio, 32.6; P = 6.9 × 10(-7)), high blood eosinophil counts (odds ratio, 9.1; P = 2.6 × 10(-6)), and rhinitis (odds ratio, 8.3; P = 4.1 × 10(-6)) compared with TH2-low subjects. Nasal IL13 expression levels were 3.9-fold higher in asthmatic participants who experienced an asthma exacerbation in the past year (P = .01). Several differentially expressed nasal genes were specific to asthma and independent of atopic status.

CONCLUSION

Nasal airway gene expression profiles largely recapitulate expression profiles in the lung airways. Nasal expression profiling can be used to identify subjects with IL13-driven asthma and a TH2-skewed systemic immune response.

FTY720, an analogue of sphingosine-1-phosphate, is cardioprotective during acute injury. Whether long-term FTY720 affords cardioprotection is unknown. Here, we report the effects of oral FTY720 on ischemia/reperfusion injury and in hypomorphic apoE mice deficient in SR-BI receptor expression (ApoeR61(h/h)/SRB1(-/- mice), a model of diet-induced coronary atherosclerosis and heart failure. We added FTY720 (0.3 mg·kg(-1)·d(-1)) to the drinking water of C57BL/6J mice. After ex vivo cardiac ischemia/reperfusion injury, these mice had significantly improved left ventricular (LV) developed pressure and reduced infarct size compared with controls. Subsequently, ApoeR61(h/h)/SRB1(-/-) mice fed a high-fat diet for 4 weeks were treated or not with oral FTY720 (0.05 mg·kg(-1)·d(-1)). This sharply reduced mortality (P < 0.02) and resulted in better LV function and less LV remodeling compared with controls without reducing hypercholesterolemia and atherosclerosis. Oral FTY720 reduced the number of blood lymphocytes and increased the percentage of CD4+Foxp3+ regulatory T cells (Tregs) in the circulation, spleen, and lymph nodes. FTY720-treated mice exhibited increased TGF-β and reduced IFN-γ expression in the heart. Also, CD4 expression was increased and strongly correlated with molecules involved in natural Treg activity, such as TGF-β and GITR. Our data suggest that long-term FTY720 treatment enhances LV function and increases longevity in mice with heart failure. These benefits resulted not from atheroprotection but from systemic immunosuppression and a moderate reduction of inflammation in the heart.