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1.  Inflammatory expression profiles in monocyte-to-macrophage differentiation in patients with systemic lupus erythematosus and relationship with atherosclerosis 
Arthritis Research & Therapy  2014;16(4):R147.
Introduction
Our objectives were to examine mononuclear cell gene expression profiles in patients with systemic lupus erythematosus (SLE) and healthy controls and to compare subsets with and without atherosclerosis to determine which genes’ expression is related to atherosclerosis in SLE.
Methods
Monocytes were obtained from 20 patients with SLE and 16 healthy controls and were in vitro-differentiated into macrophages. Subjects also underwent laboratory and imaging studies to evaluate for subclinical atherosclerosis. Whole-genome RNA expression microarray was performed, and gene expression was examined.
Results
Gene expression profiling was used to identify gene signatures that differentiated patients from controls and individuals with and without atherosclerosis. In monocytes, 9 out of 20 patients with SLE had an interferon-inducible signature compared with 2 out of 16 controls. By looking at gene expression during monocyte-to-macrophage differentiation, we identified pathways which were differentially regulated between SLE and controls and identified signatures based on relevant intracellular signaling molecules which could differentiate SLE patients with atherosclerosis from controls. Among patients with SLE, we used a previously defined 344-gene atherosclerosis signature in monocyte-to-macrophage differentiation to identify patient subgroups with and without atherosclerosis. Interestingly, this signature further classified patients on the basis of the presence of SLE disease activity and cardiovascular risk factors.
Conclusions
Many genes were differentially regulated during monocyte-to-macrophage differentiation in SLE patients compared with controls. The expression of these genes in mononuclear cells is important in the pathogenesis of SLE, and molecular profiling using gene expression can help stratify SLE patients who may be at risk for development of atherosclerosis.
doi:10.1186/ar4609
PMCID: PMC4227297  PMID: 25011540
2.  Diagnosis of relevant prostate cancer using supplementary cores from magnetic resonance imaging-prompted areas following multiple failed biopsies 
Magnetic resonance imaging  2013;31(6):947-952.
OBJECTIVES
To establish the value of MRI in targeting re-biopsy for undiagnosed prostate cancer despite multiple negative biopsies, and determine clinical relevance of detected tumors.
MATERIALS AND METHODS
38 patients who underwent MRI after 2 or more negative biopsies due to continued clinical suspicion, and later underwent TRUS-guided biopsy supplemented by biopsy of suspicious areas depicted by MRI were identified. Diagnostic performance of endorectal 3T MRI in diagnosing missed cancer foci was assessed using biopsy results as the standard of reference. Ratio of positive biopsies using systematic versus MRI-prompted approaches was compared. Gleason scores of detected cancers were used as surrogate for clinical relevance.
RESULTS
34% of patients who underwent MRI before re-biopsy had prostate cancer on subsequent biopsy. The positive biopsy yield with systematic sampling was 23% versus 92% with MRI-prompted biopsies(p<0.0001). 77% of tumors were detected exclusively in the MRI-prompted zones. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of MRI to provide a positive biopsy were 92%, 60%, 55%, 94% and 71%, respectively. The anterior gland and apical regions contained most tumors; 75% of cancers detected by MRI-prompted biopsy had Gleason score≥7.
CONCLUSIONS
Clinically relevant tumors missed by multiple TRUS-guided biopsies can be detected by a MRI-prompted approach.
doi:10.1016/j.mri.2013.02.007
PMCID: PMC3676721  PMID: 23602725
4.  Hepcidin in anemia of chronic heart failure 
American journal of hematology  2011;86(1):107-109.
Anemia is a common finding among patients with chronic heart failure. Although co-morbidities, such as kidney failure, might contribute to the pathogenesis of anemia, many patients with heart failure do not have any other obvious etiology for their anemia. We investigated whether anemia in heart failure is associated with an elevation in hepcidin concentration.
We used time-of-flight mass spectrometry to measure hepcidin concentration in urine and serum samples of patients with heart failure and in control subjects. We found that the concentration of hepcidin was lower in urine samples of patients with heart failure compared to those of control subjects. Serum hepcidin was also reduced in heart failure but was not significantly lower than that in controls. There were no significant differences between hepcidin levels in patients with heart failure and anemia compared to patients with heart failure and normal hemoglobin. We concluded that hepcidin probably does not play a major role in pathogenesis of anemia in patients with chronic heart failure.
doi:10.1002/ajh.21902
PMCID: PMC3076004  PMID: 21080339
Anemias; Cytokines; Iron
5.  The Challenge of Problem Residents 
Internal medicine residency training is demanding and residents can experience a wide variety of professional and personal difficulties. Residency programs everywhere have had and will continue to have problem residents. Training programs should be equipped to effectively identify and manage residents who experience problems. Previous articles that have been published on the topic of problem residents primarily addressed concerns such as impairment due to depression and substance abuse. The content of this article is derived from a comprehensive review of the literature as well as other data sources such as interviews with program directors and workshops at national professional meetings. This article focuses primarily on four issues related to problem residents: their identification, underlying causes, management, and prevention. The study attempts to be evidence-based, wherever possible, highlighting what is known. Recommendations based on the synthesis of the data are also made. Future ongoing studies of problem residents will improve our understanding of the matters involved, and may ultimately lead to improved outcomes for these trainees.
doi:10.1046/j.1525-1497.2001.016007486.x
PMCID: PMC1495245  PMID: 11520388
medical education; internship; residency; problem resident

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