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1.  Learning by doing: observing an interprofessional process as an interprofessional team 
Journal of interprofessional care  2013;28(3):249-251.
New competencies exist for interprofessional education, which are centered on the goal of improving quality of care and patient safety through improved interprofessional collaboration. Interprofessional education and effective interprofessional collaboration are cornerstones of the Veterans Affairs Quality Scholars fellowship program. The purpose of this project was to evaluate an innovative interprofessional education strategy in which teams of physicians and nurses were “learning by doing” as they observed and analyzed the functioning of an interprofessional process, specifically, inpatient discharge. Fellows completed voluntary, anonymous surveys seeking their perspectives about the project. Fellows’ feedback revealed several themes, with both positive and negative characteristics related to team functioning, interprofessional understanding, microsystem knowledge, pooled knowledge and assignment challenges. The strength of this strategy is exemplified by the fact that fellows not only learned from each other’s separate professional observations, but also observed the emergence of a shared interprofessional perspective through working together.
PMCID: PMC4289149  PMID: 24070019
Interprofessional collaboration; interprofessional education; interprofessional evaluation; teams
2.  Documenting Quality Improvement and Patient Safety Efforts: The Quality Portfolio. A Statement from the Academic Hospitalist Taskforce 
Physicians increasingly investigate, work, and teach to improve the quality of care and safety of care delivery. The Society of General Internal Medicine Academic Hospitalist Task Force sought to develop a practical tool, the quality portfolio, to systematically document quality and safety achievements. The quality portfolio was vetted with internal and external stakeholders including national leaders in academic medicine. The portfolio was refined for implementation to include an outlined framework, detailed instructions for use and an example to guide users. The portfolio has eight categories including: (1) a faculty narrative, (2) leadership and administrative activities, (3) project activities, (4) education and curricula, (5) research and scholarship, (6) honors, awards, and recognition, (7) training and certification, and (8) an appendix. The authors offer this comprehensive, yet practical tool as a method to document quality and safety activities. It is relevant for physicians across disciplines and institutions and may be useful as a standalone document or as an adjunct to traditional promotion documents. As the Next Accreditation System is implemented, academic medical centers will require faculty who can teach and implement the systems-based practice requirements. The quality portfolio is a method to document quality improvement and safety activities.
Electronic supplementary material
The online version of this article (doi:10.1007/s11606-013-2532-z) contains supplementary material, which is available to authorized users.
PMCID: PMC3889978  PMID: 23807726
quality portfolio; quality improvement; patient safety; academic medicine; career development; quality of health care
3.  In vitro evaluation of bi-layer silk fibroin scaffolds for gastrointestinal tissue engineering 
Journal of Tissue Engineering  2014;5:2041731414556849.
Silk fibroin scaffolds were investigated for their ability to support attachment, proliferation, and differentiation of human gastrointestinal epithelial and smooth muscle cell lines in order to ascertain their potential for tissue engineering. A bi-layer silk fibroin matrix composed of a porous silk fibroin foam annealed to a homogeneous silk fibroin film was evaluated in parallel with small intestinal submucosa scaffolds. AlamarBlue analysis revealed that silk fibroin scaffolds supported significantly higher levels of small intestinal smooth muscle cell, colon smooth muscle cell, and esophageal smooth muscle cell attachment in comparison to small intestinal submucosa. Following 7 days of culture, relative numbers of each smooth muscle cell population maintained on both scaffold groups were significantly elevated over respective 1-day levels—indicative of cell proliferation. Real-time reverse transcription polymerase chain reaction and immunohistochemical analyses demonstrated that both silk fibroin and small intestinal submucosa scaffolds were permissive for contractile differentiation of small intestinal smooth muscle cell, colon smooth muscle cell, esophageal smooth muscle cell as determined by significant upregulation of α-smooth muscle actin and SM22α messenger RNA and protein expression levels following transforming growth factor-β1 stimulation. AlamarBlue analysis demonstrated that both matrix groups supported similar degrees of attachment and proliferation of gastrointestinal epithelial cell lines including colonic T84 cells and esophageal epithelial cells. Following 14 days of culture on both matrices, spontaneous differentiation of T84 cells toward an enterocyte lineage was confirmed by expression of brush border enzymes, lactase, and maltase, as determined by real-time reverse transcription polymerase chain reaction and immunohistochemical analyses. In contrast to small intestinal submucosa scaffolds, silk fibroin scaffolds supported spontaneous differentiation of esophageal epithelial cells toward a suprabasal cell lineage as indicated by significant upregulation of cytokeratin 4 and cytokeratin 13 messenger RNA transcript levels. In addition, esophageal epithelial cells maintained on silk fibroin scaffolds also produced significantly higher involucrin messenger RNA transcript levels in comparison to small intestinal submucosa counterparts, indicating an increased propensity for superficial, squamous cell specification. Collectively, these data provide evidence for the potential of silk fibroin scaffolds for gastrointestinal tissue engineering applications.
PMCID: PMC4228923  PMID: 25396043
Colon; esophagus; small intestine; silk fibroin; tissue engineering
4.  Rapid Antigen Group A Streptococcus Test to Diagnose Pharyngitis: A Systematic Review and Meta-Analysis 
PLoS ONE  2014;9(11):e111727.
Pharyngitis management guidelines include estimates of the test characteristics of rapid antigen streptococcus tests (RAST) using a non-systematic approach.
To examine the sensitivity and specificity, and sources of variability, of RAST for diagnosing group A streptococcal (GAS) pharyngitis.
Data Sources
MEDLINE, Cochrane Reviews, Centre for Reviews and Dissemination, Scopus, SciELO, CINAHL, guidelines, 2000–2012.
Study Selection
Culture as reference standard, all languages.
Data Extraction and Synthesis
Study characteristics, quality.
Main Outcome(s) and Measure(s)
Sensitivity, specificity.
We included 59 studies encompassing 55,766 patients. Forty three studies (18,464 patients) fulfilled the higher quality definition (at least 50 patients, prospective data collection, and no significant biases) and 16 (35,634 patients) did not. For the higher quality immunochromatographic methods in children (10,325 patients), heterogeneity was high for sensitivity (inconsistency [I2] 88%) and specificity (I2 86%). For enzyme immunoassay in children (342 patients), the pooled sensitivity was 86% (95% CI, 79–92%) and the pooled specificity was 92% (95% CI, 88–95%). For the higher quality immunochromatographic methods in the adult population (1,216 patients), the pooled sensitivity was 91% (95% CI, 87 to 94%) and the pooled specificity was 93% (95% CI, 92 to 95%); however, heterogeneity was modest for sensitivity (I2 61%) and specificity (I2 72%). For enzyme immunoassay in the adult population (333 patients), the pooled sensitivity was 86% (95% CI, 81–91%) and the pooled specificity was 97% (95% CI, 96 to 99%); however, heterogeneity was high for sensitivity and specificity (both, I2 88%).
RAST immunochromatographic methods appear to be very sensitive and highly specific to diagnose group A streptococcal pharyngitis among adults but not in children. We could not identify sources of variability among higher quality studies. The present systematic review provides the best evidence for the wide range of sensitivity included in current guidelines.
PMCID: PMC4219770  PMID: 25369170
5.  Bladder Tissue Regeneration Using Acellular Bi-Layer Silk Scaffolds in a Large Animal Model of Augmentation Cystoplasty 
Biomaterials  2013;34(34):10.1016/j.biomaterials.2013.08.001.
A cellular scaffolds derived from Bombyx mori silk fibroin were investigated for their ability to support functional tissue regeneration in a porcine model of augmentation cystoplasty. Two bi-layer matrix configurations were fabricated by solvent-casting/salt leaching either alone (Group 1) or in combination with silk film casting (Group 2) to yield porous foams buttressed by heterogeneous surface pore occlusions or homogenous silk films, respectively. Bladder augmentation was performed with each scaffold group (6×6cm2) in juvenile Yorkshire swine for 3 m of implantation. Augmented animals exhibited high rates of survival (Group 1: 5/6, 83%; Group 2: 4/4, 100%) and voluntary voiding over the course of the study period. Urodynamic evaluations demonstrated mean increases in bladder capacity over pre-operative levels (Group 1: 277%; Group 2: 153%) which exceeded non surgical control gains (144%) encountered due to animal growth. Similarly, elevations in bladder compliance were substantially higher in augmented animals from baseline (Group 1: 357%; Group 2: 147%) in comparison to controls (41%). Gross tissue evaluations revealed that both matrix configurations supported extensive de novo tissue formation throughout the entire original implantation site which exhibited ultimate tensile strength similar to nonsurgical counterparts. Histological and immunohistochemical analyses showed that both implant groups promoted comparable extents of smooth muscle regeneration and contractile protein (α-smooth muscle actin and SM22α) expression within defect sites similar to controls. Parallel evaluations demonstrated the formation of a transitional, multi-layered urothelium with prominent cytokeratin, uroplakin, and p63 protein expression in both matrix groups. De novo innervation and vascularization processes were evident in all regenerated tissues indicated by synaptophysin-positive neuronal cells and vessels lined with CD31 expressing endothelial cells. Ex vivo organ bath studies demonstrated that regenerated tissues supported by both silk matrices displayed contractile responses to carbachol, α,β-methylene-ATP, KCl, and electrical field stimulation similar to controls. Our data detail the ability of acellular silk scaffolds to support regeneration of innervated, vascularized smooth muscle and urothelial tissues within 3 m with structural, mechanical, and functional properties comparable to native tissue in a porcine model of bladder repair.
PMCID: PMC3810021  PMID: 23953839
silk; tissue engineering; bladder; wound healing
6.  A 76-Year-Old Woman with Diaphoresis and Anxiety 
Journal of General Internal Medicine  2013;28(10):1376-1380.
PMCID: PMC3785657  PMID: 23729373
7.  Bedside Hand Grip Assessment with the Sphygmomanometer 
PMCID: PMC3785662  PMID: 23568188
physical examination; hand Strength; muscle strength dynamometer
8.  Trypanosomatids topoisomerase re-visited. New structural findings and role in drug discovery 
Graphical abstract
•There is an urgent need of new treatments against trypanosomatids-borne diseases.•DNA topoisomerases are pointed as potential drug targets against unicellular parasites.•Trypanosomatids have a full set of DNA topoisomerases in both nucleus and kinetoplast.•TopII and TopIII are located in the kinetoplast and fully involved in kDNA replication.•Tritryps TopIB differ in structure from mammalian’s pointing to an attractive target.
The Trypanosomatidae family, composed of unicellular parasites, causes severe vector-borne diseases that afflict human populations worldwide. Chagas disease, sleeping sickness, as well as different sorts of leishmaniases are amongst the most important infectious diseases produced by Trypanosoma cruzi, Trypanosoma brucei and Leishmania spp., respectively. All these infections are closely related to weak health care services in low-income populations of less developed and least economically developed countries. Search for new therapeutic targets in order to hit these pathogens is of paramount priority, as no effective vaccine is currently in use against any of these parasites. Furthermore, present-day chemotherapy comprises old-fashioned drugs full of important side effects. Besides, they are prone to produce tolerance and resistance as a consequence of their continuous use for decades. DNA topoisomerases (Top) are ubiquitous enzymes responsible for solving the torsional tensions caused during replication and transcription processes, as well as in maintaining genomic stability during DNA recombination. As the inhibition of these enzymes produces cell arrest and triggers cell death, Top inhibitors are among the most effective and most widely used drugs in both cancer and antibacterial therapies. Top relaxation and decatenation activities, which are based on a common nicking–closing cycle involving one or both DNA strands, have been pointed as a promising drug target. Specific inhibitors that bind to the interface of DNA-Top complexes can stabilize Top-mediated transient DNA breaks. In addition, important structural differences have been found between Tops from the Trypanosomatidae family members and Tops from the host. Such dissimilarities make these proteins very interesting for drug design and molecular intervention. The present review is a critical update of the last findings regarding trypanosomatid’s Tops, their new structural features, their involvement both in the physiology and virulence of these parasites, as well as their use as promising targets for drug discovery.
PMCID: PMC4266802  PMID: 25516844
Top, DNA topoisomerase; CL, cutaneous leishmaniasis; VL, visceral leishmaniasis; DALYs, disability-adjusted life years; kDNA, kinetoplast DNA; NTD, neglected tropical diseases; NGO, non-governmental organization; lk, linking number; NLS, Nuclear Localization Signal; Kinetoplastids; Tritryps; Topoisomerases; DNA topology; Target-based drug discovery; Chemotherapy
9.  The Performance of Silk Scaffolds in a Rat Model of Augmentation Cystoplasty 
Biomaterials  2013;34(20):4758-4765.
The diverse processing plasticity of silk-based biomaterials offers a versatile platform for understanding the impact of structural and mechanical matrix properties on bladder regenerative processes. Three distinct groups of 3-D matrices were fabricated from aqueous solutions of Bombyx mori silk fibroin either by a gel spinning technique (GS1 and GS2 groups) or a solvent-casting/salt-leaching method in combination with silk film casting (FF group). SEM analyses revealed that GS1 matrices consisted of smooth, compact multi-laminates of parallel-oriented silk fibers while GS2 scaffolds were composed of porous (pore size range, 5–50µm) lamellar-like sheets buttressed by a dense outer layer. Bi-layer FF scaffolds were comprised of porous foams (pore size, ~400 µm) fused on their external face with a homogenous, nonporous silk film. Silk groups and small intestinal submucosa (SIS) matrices were evaluated in a rat model of augmentation cystoplasty for 10 weeks of implantation and compared to cystotomy controls. Gross tissue evaluations revealed the presence of intra-luminal stones in all experimental groups. The incidence and size of urinary calculi was the highest in animals implanted with gel spun silk matrices and SIS with frequencies ≥57% and stone diameters of 3–4mm. In contrast, rats augmented with FF scaffolds displayed substantially lower rates (20%) and stone size (2mm), similar to the levels observed in controls (13%, 2mm). Histological (hematoxylin and eosin, Masson's trichrome) and immunohistochemical (IHC) analyses showed comparable extents of smooth muscle regeneration and contractile protein (α-smooth muscle actin and SM22α) expression within defect sites supported by all matrix groups similar to controls. Parallel evaluations demonstrated the formation of a transitional, multi-layered urothelium with prominent uroplakin and p63 protein expression in all experimental groups. De novo innervation and vascularization processes were evident in all regenerated tissues indicated by Fox3-positive neuronal cells and vessels lined with CD31 expressing endothelial cells. In comparison to other biomaterial groups, cystometric analyses at 10 weeks post-op revealed that animals implanted with the FF matrix configuration displayed superior urodynamic characteristics including compliance, functional capacity, as well as spontaneous non voiding contractions consistent with control levels. Our data demonstrate that variations in scaffold processing techniques can influence the in vivo functional performance of silk matrices in bladder reconstructive procedures.
PMCID: PMC3676949  PMID: 23545287
silk; bladder tissue engineering; bladder; wound healing
11.  Hydroxyethyl starch in severe sepsis: end of starch era? 
Critical Care  2013;17(2):310.
Expanded abstract
Perner A, Haase N, Guttormsen AB, Tenhunen J, Klemenzson G, Åneman A, Madsen KR, Møller MH, Elkjær JM, Poulsen LM, Bendtsen A, Winding R, Steensen M, Berezowicz P, Søe-Jensen P, Bestle M, Strand K, Wiis J, White JO, Thornberg KJ, Quist L, Nielsen J, Andersen LH, Holst LB, Thormar K, Kjældgaard AL, Fabritius ML, Mondrup F, Pott FC, Møller TP, Winkel P, Wetterslev J; 6S Trial Group; Scandinavian Critical Care Trials Group: Hydroxyethyl starch 130/0.42 versus Ringer's acetate in severe sepsis. N Engl J Med 2012, 367:124-34.
Hydroxyethyl starch (HES) is widely used for fluid resuscitation in ICUs, but its safety and efficacy have not been established in patients with severe sepsis.
To assess the effects of HES 130/0.4 compared with a balanced crystalloid solution on mortality and end-stage kidney failure in patients with severe sepsis.
Multicenter, parallel-group, blinded, randomized clinical trial, in patients with severe sepsis.
Patients with severe sepsis admitted to the ICU received fluid resuscitation with either 6% HES 130/0.42 (Tetraspan) or Ringer's acetate at a dose of up to 33 ml per kilogram of ideal body weight per day.
Of the 804 patients who underwent randomization, 798 were included in the modified intention-to-treat population. The two intervention groups had similar baseline characteristics. At 90 days after randomization, 201 of 398 patients (51%) assigned to HES 130/0.42 had died, as compared with 172 of 400 patients (43%) assigned to Ringer's acetate (relative risk, 1.17; 95% confidence interval (CI), 1.01 to 1.36; P = 0.03); 1 patient in each group had end-stage kidney failure. In the 90-day period, 87 patients (22%) assigned to HES 130/0.42 were treated with renal replacement therapy versus 65 patients (16%) assigned to Ringer's acetate (relative risk, 1.35; 95% CI, 1.01 to 1.80; P = 0.04), and 38 patients (10%) and 25 patients (6%), respectively, had severe bleeding (relative risk, 1.52; 95% CI, 0.94 to 2.48; P = 0.09). The results were supported by multivariate analyses, with adjustment for known risk factors for death or acute kidney injury at baseline.
Patients with severe sepsis assigned to fluid resuscitation with HES 130/0.42 had an increased risk of death at day 90 and were more likely to require renal replacement therapy compared with those receiving Ringer's acetate.
PMCID: PMC3672539  PMID: 23509901
12.  The Department of Veterans Affairs National Quality Scholars Fellowship Program 
The Department of Veterans Affairs National Quality Scholars Fellowship Program (VAQS) was established in 1998 as a post-graduate medical education fellowship to train physicians in new methods of improving the quality and safety of health care for Veterans and the nation. The VAQS curriculum is based on adult learning theory, with a national core curriculum of face-to-face components, technologically mediated distance learning components, and a unique local curriculum that draws from the strengths of regional resources.
VAQS has established strong ties with other VA programs. Fellows’ research and projects are integrated with local and regional VA leaders’ priorities, enhancing the relevance and visibility of the fellows’ efforts and promoting recruitment of fellows to VA positions.
VAQS has enrolled 96 fellows from 1999 to 2008; 75 have completed the program and 11 are currently enrolled. Fellowship graduates have pursued a variety of career paths: 20% are continuing training (most in VA); 32% hold a VA faculty/staff position; 63% are academic faculty; and 80% conduct clinical or research work related to health care improvement. Graduates have held leadership positions in VA, Department of Defense, and public health.
Combining knowledge about the improvement of health care with adult learning strategies, distance learning technologies, face-to-face meetings, local mentorship, and experiential projects has been successful in improving care in VA and preparing physicians to participate in, study, and lead the improvement of health care quality and safety.
PMCID: PMC3800745  PMID: 19940583
13.  Quality of Diabetes Mellitus Care by Rural Primary Care Physicians 
To explore the relationship between degree of rurality and glucose (hemoglobin A1c), blood pressure (BP), and lipid (LDL) control among patients with diabetes.
Descriptive study; 1,649 patients in 205 rural practices in the United States. Patients’ residence ZIP codes defined degree of rurality (Rural-Urban Commuting Areas codes). Outcomes were measures of acceptable control (A1c <= 9%, BP < 140/90 mmHg, LDL < 130 mg/dL) and optimal control (A1c < 7%, BP < 130/80 mmHg, LDL < 100 mg/dL). Statistical significance was set at P < .008 (Bonferroni’s correction).
Although the proportion of patients with reasonable A1c control worsened by increasing degree of rurality, the differences were not statistically significant (urban 90%, large rural 88%, small rural 85%, isolated rural 83%; P = .10); mean A1c values also increased by degree of rurality, although not statistically significant (urban 7.2 [SD 1.6], large rural 7.3 [SD 1.7], small rural 7.5 [SD1.8], isolated rural 7.5 [SD1.9]; P = .16). We observed no differences between degree of rural and reasonable BP or LDL control (P = .42, P = .23, respectively) or optimal A1c or BP control (P = .52, P = .65, respectively). Optimal and mean LDL values worsened as rurality increased (P = .08, P = .029, respectively).
In patients with diabetes who seek care in the rural Southern US, we observed no relationship between degree of rurality of patients’ residence and traditional measures of quality of care. Further examination of the trends and explanatory factors for relative worsening of metabolic control by increasing degree of rurality is warranted.
PMCID: PMC3481192  PMID: 23083082
family medicine; health disparities; internal medicine; medical care; quality
14.  Buyers Beware: Lead Poisoning due to Ayurvedic Medicine 
Journal of General Internal Medicine  2012;27(10):1384-1386.
A 29-year-old man, who recently emigrated from India, presented with a 2-week history of abdominal pain, as well as nausea, constipation, and fatigue. He underwent removal of a parathyroid adenoma 6 weeks prior to admission and received a locally made Indian traditional medicine (Ayurveda) for pain control; however, this information was not initially available. He was instructed to take approximately 15 g/day. Initial evaluation revealed a normocytic anemia, but other workup including imaging and endoscopy was unrevealing. Given his recent use of Ayurvedic medicines, we tested for lead poisoning and found a blood lead level of 72 mcg/dl. We sent his medicine for analysis and found it had a high lead concentration of 36,000 mcg/g, which is over 25,000 times the maximum daily dose. He improved with cessation of the medicine and treatment with succimer. Lead poisoning can present with a variety of nonspecific signs and symptoms, including abdominal pain and anemia. Ayurvedic medicines, as well as traditional medicines from other cultures, may be a source of lead or other heavy metals. It is essential for physicians to be aware of adverse effects of Ayurvedic medicines as they are easily available and increasing in popularity.
PMCID: PMC3445671  PMID: 22476953
dietary supplements; lead; India; medicine; Ayurvedic; Phytotherapy; plant extracts/chemistry
15.  Use of Ecological Momentary Assessment to Determine Which Structural Factors Impact Perceived Teaching Quality of Attending Rounds 
Providing high-quality teaching to residents during attending rounds is challenging. Reasons include structural factors that affect rounds, which are beyond the attending's teaching style and control.
To develop a new evaluation tool to identify the structural components of ward rounds that most affect teaching quality in an internal medicine (IM) residency program.
The authors developed a 10-item Ecological Momentary Assessment (EMA) tool and collected daily evaluations for 18 months from IM residents rotating on inpatient services. Residents ranked the quality of teaching on rounds that day, and questions related to their service (general medicine, medical intensive care unit, and subspecialty services), patient census, absenteeism of team members, call status, and number of teaching methods used by the attending.
Residents completed 488 evaluation cards over 18 months. This found no association between perceived teaching quality and training level, team absenteeism, and call status. We observed differences by service (P < .001) and patient census (P  =  .009). After adjusting for type of service, census was no longer significant. Use of a larger variety of teaching methods was associated with higher perceived teaching quality, regardless of service or census (P for trend < .001).
The EMA tool successfully identified that higher patient census was associated with lower perceived teaching quality, but the results were also influenced by the type of teaching service. We found that, regardless of census or teaching service, attendings can improve their teaching by diversifying the number of methods used in daily rounds.
PMCID: PMC3444185  PMID: 23997876
16.  Evaluation of Gel Spun Silk-Based Biomaterials in a Murine Model of Bladder Augmentation 
Biomaterials  2010;32(3):808-818.
Currently, gastrointestinal segments are considered the gold standard for bladder reconstructive procedures. However, significant complications including chronic urinary tract infection, metabolic abnormalities, urinary stone formation, bowel dysfunction, and secondary malignancies are associated with this approach. Biomaterials derived from silk fibroin may represent a superior alternative due their robust mechanical properties, biodegradable features, and processing plasticity. In the present study, we evaluated the efficacy of a gel spun silk-based matrix for bladder augmentation in a murine model. Over the course of 70 d implantation period, H&E and Masson’s trichrome (MTS) analysis revealed that silk matrices were capable of supporting both urothelial and smooth muscle regeneration at the defect site. Prominent uroplakin and contractile protein expression (α-actin, calponin, and SM22α) was evident by immunohistochemical analysis demonstrating maturation of the reconstituted bladder wall compartments. Gel spun silk matrices also elicited a minimal acute inflammatory reaction following 70 d of bladder integration, in contrast to parallel assessments of small intestinal submucosa (SIS) and polyglycolic acid (PGA) matrices which routinely promoted evidence of fibrosis and chronic inflammatory responses. Voided stain on paper analysis revealed that silk augmented animals displayed similar voiding patterns in comparison to non surgical controls by 42 d of implantation. In addition, cystometric evaluations of augmented bladders at 70 d post-op demonstrated that silk scaffolds supported significant increases in bladder capacity, voided volume, and flow rate while maintaining similar degrees of compliance relative to the control group. These results provide evidence for the utility of gel spun silk-based matrices for functional bladder tissue engineering applications.
PMCID: PMC3742077  PMID: 20951426
silk; bladder tissue engineering; smooth muscle cell; SIS; Polyglycolic acid
17.  A 60-Year-Old Woman with Chorea and Weight Loss 
PMCID: PMC3358395  PMID: 22143453
diagnostic reasoning; clinical problem solving; dual process theory; illness scripts; chorea; paraneoplastic syndrome
18.  Evaluation of Silk Biomaterials in Combination with Extracellular Matrix Coatings for Bladder Tissue Engineering with Primary and Pluripotent Cells 
PLoS ONE  2013;8(2):e56237.
Silk-based biomaterials in combination with extracellular matrix (ECM) coatings were assessed as templates for cell-seeded bladder tissue engineering approaches. Two structurally diverse groups of silk scaffolds were produced by a gel spinning process and consisted of either smooth, compact multi-laminates (Group 1) or rough, porous lamellar-like sheets (Group 2). Scaffolds alone or coated with collagen types I or IV or fibronectin were assessed independently for their ability to support attachment, proliferation, and differentiation of primary cell lines including human bladder smooth muscle cells (SMC) and urothelial cells as well as pluripotent cell populations, such as murine embryonic stem cells (ESC) and induced pluripotent stem (iPS) cells. AlamarBlue evaluations revealed that fibronectin-coated Group 2 scaffolds promoted the highest degree of primary SMC and urothelial cell attachment in comparison to uncoated Group 2 controls and all Group 1 scaffold variants. Real time RT-PCR and immunohistochemical (IHC) analyses demonstrated that both fibronectin-coated silk groups were permissive for SMC contractile differentiation as determined by significant upregulation of α-actin and SM22α mRNA and protein expression levels following TGFβ1 stimulation. Prominent expression of epithelial differentiation markers, cytokeratins, was observed in urothelial cells cultured on both control and fibronectin-coated groups following IHC analysis. Evaluation of silk matrices for ESC and iPS cell attachment by alamarBlue showed that fibronectin-coated Group 2 scaffolds promoted the highest levels in comparison to all other scaffold formulations. In addition, real time RT-PCR and IHC analyses showed that fibronectin-coated Group 2 scaffolds facilitated ESC and iPS cell differentiation toward both urothelial and smooth muscle lineages in response to all trans retinoic acid as assessed by induction of uroplakin and contractile gene and protein expression. These results demonstrate that silk scaffolds support primary and pluripotent cell responses pertinent to bladder tissue engineering and that scaffold morphology and fibronectin coatings influence these processes.
PMCID: PMC3567020  PMID: 23409160
19.  Selecting the Best Clinical Vignettes for Academic Meetings: Should the Scoring Tool Criteria be Modified? 
The performance of scoring tools to select clinical vignettes for presentation at academic meetings has never been assessed.
To measure the psychometric properties of two scoring tools used to select clinical vignettes and to determine which elements are most helpful.
Prospective observational study.
Participants submitting clinical vignette abstracts, Society of General Internal Medicine annual meetings (2006–2007).
The 2006 scoring tool had three criteria (clarity, significance, and relevance) with brief general descriptors. The 2007 modified tool had five criteria (clarity, significance, relevance, teaching value, and overall assessment) with more detailed descriptors.
A total of 938 clinical vignette abstracts were submitted (484 in 2006; 454 in 2007); 59.5% (n = 288) were accepted for presentation. Cronbach’s alpha was 0.81 for the 2006 three-item tool and 0.95 for the 2007 modified five-item tool. Simplifying the five-item 2007 tool to three items (relevance, teaching value, overall assessment) yielded a Cronbach’s alpha of 0.95. The agreement between the number of clinical vignettes accepted for presentation (2007) using the average score of the five items with the number that would have been accepted using the simplified three items (relevance, teaching value, overall assessment) was almost perfect, with kappa 0.89 (95% confidence interval, 0.85 to 0.93).
Both scoring tools performed well, but a simplified tool with three items (relevance, teaching value, and overall assessment) and detailed descriptors was optimal; the simplified tool could improve the reviewer efficiency and quality of clinical vignettes presented at national meetings.
PMCID: PMC3270243  PMID: 21927965
professional competence; internship and residency; education medical/methods; educational measurement/methods/standards; congresses as topic; reproducibility of results
20.  Draft Genome of Streptomyces tsukubaensis NRRL 18488, the Producer of the Clinically Important Immunosuppressant Tacrolimus (FK506) 
Journal of Bacteriology  2012;194(14):3756-3757.
The macrocyclic polyketide tacrolimus (FK506) is a potent immunosuppressant that prevents T-cell proliferation produced solely by Streptomyces species. We report here the first draft genome sequence of a true FK506 producer, Streptomyces tsukubaensis NRRL 18488, the first tacrolimus-producing strain that was isolated and that contains the full tacrolimus biosynthesis gene cluster.
PMCID: PMC3393489  PMID: 22740677
21.  A multimethod approach for cross-cultural training in an internal medicine residency program 
Medical Education Online  2013;18:10.3402/meo.v18i0.20352.
Cultural competence training in residency is important to improve learners’ confidence in cross-cultural encounters. Recognition of cultural diversity and avoidance of cultural stereotypes are essential for health care providers.
We developed a multimethod approach for cross-cultural training of Internal Medicine residents and evaluated participants’ preparedness for cultural encounters. The multimethod approach included (1) a conference series, (2) a webinar with a national expert, (3) small group sessions, (4) a multicultural social gathering, (5) a Grand Rounds presentation on cross-cultural training, and (6) an interactive, online case-based program.
The program had 35 participants, 28 of whom responded to the survey. Of those, 16 were white (62%), and residents comprised 71% of respondents (n=25). Following training, 89% of participants were more comfortable obtaining a social history. However, prior to the course only 27% were comfortable caring for patients who distrust the US system and 35% could identify religious beliefs and customs which impact care. Most (71%) believed that the training would help them give better care for patients from different cultures, and 63% felt more comfortable negotiating a treatment plan following the course.
Multimethod training may improve learners’ confidence and comfort with cross-cultural encounters, as well as lay the foundation for ongoing learning. Follow-up is needed to assess whether residents’ perceived comfort will translate into improved patient outcomes.
PMCID: PMC3657071  PMID: 23683845
cultural competence; residency education; community resources; web-based curriculum; racial disparities; internal medicine
22.  Preparing for Oral Scientific and Clinical Vignette Presentations 
Little is known about how faculty, residents, and fellows practice for oral presentations at academic meetings. We sought to categorize presenters' practice styles and the impact of feedback.
We surveyed oral presenters at 5 annual academic general internal medicine meetings between 2008 and 2010, using a cross-sectional design. Main measures were frequency and settings of practice, most helpful practice setting, changes made in response to feedback, impact of feedback, and perceived quality of presentation.
The response rate was 63% (333/525 responders). Respondents represented 59 academic medical centers. Presenters reported practicing in a mean ± SD of 2.3 (±1.3) of 5 different settings. Of the 46% of presenters (152/333) who practiced in front of a group of more experienced colleagues, 80% of presenters (122/152) reported it was the most helpful setting. Eighty-one percent of presenters (268/333) practiced alone, and 25% of presenters (82/333) reported practicing alone was the most helpful setting. The mean numbers of change types reported by faculty were fewer than those reported by residents and fellows (mean 2.3 ± 1.8, and 3.1 ± 2.0, respectively; P < .001). Practicing alone was not associated with changes in content (P  =  .30), visual aids (P  =  .12), or delivery style (P  =  .53).
Practicing in front of a group of experienced colleagues was the most helpful setting in which to prepare for an oral academic meeting presentation, but it was not universally utilized. Feedback given at these sessions was more likely to result in changes made to the presentation; however, broader implementation of such sessions 5 require institutional support.
PMCID: PMC3244325  PMID: 23205208
23.  A web-based diabetes intervention for physician: a cluster-randomized effectiveness trial 
To determine the effectiveness of a provider-based education and implementation intervention for improving diabetes control.
Cluster-randomized trial with baseline and follow-up cross sections of diabetes patients in each participating physician's practice.
Eleven US Southeastern states, 2006–08.
Two hundred and five rural primary care physicians.
Multi-component interactive intervention including Web-based continuing medical education, performance feedback and quality improvement tools.
Primary Outcome Measures
‘Acceptable control’ [hemoglobin A1c ≤9%, blood pressure (BP) <140/90 mmHg, low-density lipoprotein cholesterol (LDL) <130 mg/dl] and ‘optimal control’ (A1c <7%, BP <130/80 mmHg, LDL <100 mg/dl).
Of 364 physicians attempting to register, 205 were randomized to the intervention (n= 102) or control arms (n= 103). Baseline and follow-up data were provided by 95 physicians (2127 patients). The proportion of patients with A1c ≤9% was similar at baseline and follow-up in both the control [adjusted odds ratio (AOR): 0.94; 95% confidence interval (CI): 0.61, 1.47] and intervention arms [AOR: 1.16 (95% CI: 0.80, 1.69)]; BP <140/90 mmHg and LDL <130 mg/dl were also similar at both measurement points (P= 0.66, P= 0.46; respectively). We observed no significant effect on diabetes control attributable to the intervention for any of the primary outcome measures. Intervention physicians engaged with the Website over a median of 64.7 weeks [interquartile range (IQR): 45.4–81.8) for a median total of 37 min (IQR: 16–66).
A wide-reach, low-intensity, Web-based interactive multi-component intervention did not improve control of glucose, BP or lipids for patients with diabetes of physicians practicing in the rural Southeastern US.
PMCID: PMC3247785  PMID: 21831967
internet; translational research; diabetes mellitus; rural health services; education; medical; continuing process assessment (Health Care)
CME providers may be interested in identifying effective marketing strategies to direct users to specific content. The use of online advertisements to recruit participants for clinical trials, public health programs, and Continuing Medical Education (CME) has been shown to be effective in some but not all studies. The purpose of this study was to compare the impact of two marketing strategies in the context of an online CME cultural competence curriculum (
In an interrupted time-series quasi-experimental design, two marketing strategies were tested: a) wide dissemination to relevant organizations over a period of approximately four months, and b) Internet paid search using Google Ads (five consecutive eight-week periods--control 1, cultural/ CME advertisement, control 2, hypertension/ content advertisement, control 3). Outcome measures were CME credit requests, Web traffic (visits per day, page views, pages viewed per visit), and cost.
Overall, the site was visited 19,156 times and 78,160 pages were viewed. During the wide dissemination phase, the proportion of visits requesting CME credit decreased between the first (5.3%) and second halves (3.3%) of this phase (p= .04). During the Internet paid search phase, the proportion of visits requesting CME credit was highest during the cultural/ CME advertisement period (control 1, 1.4%; cultural/CME ad, 4.3%; control 2, 1.5%; hypertension/content ad, 0.6%; control 3, 0.8%; p<.001). All measures of Web traffic changed during the Internet paid search phase (p<.01); however, changes were independent of the advertisement periods. The incremental cost for the cultural advertisement per CME credit requested was $0.64US.
Internet advertisement focusing on cultural competence and CME was associated with about a three-fold increase in requests for CME credit at an incremental cost of under $1; however, Web traffic changes were independent of the advertisement strategy.
PMCID: PMC3500657  PMID: 21425356
Marketing; Continuing Medical Education; Internet; Web; Online; Cultural Competence
25.  Important role of CCR2 in a murine model of coronary vasculitis 
BMC Immunology  2012;13:56.
Chemokines and their receptors play a role in the innate immune response as well as in the disruption of the balance between pro-inflammatory Th17 cells and regulatory T cells (Treg), underlying the pathogenesis of coronary vasculitis in Kawasaki disease (KD).
Here we show that genetic inactivation of chemokine receptor (CCR)-2 is protective against the induction of aortic and coronary vasculitis following injection of Candida albicans water-soluble cell wall extracts (CAWS). Mechanistically, both T and B cells were required for the induction of vasculitis, a role that was directly modulated by CCR2. CAWS administration promoted mobilization of CCR2-dependent inflammatory monocytes (iMo) from the bone marrow (BM) to the periphery as well as production of IL-6. IL-6 was likely to contribute to the depletion of Treg and expansion of Th17 cells in CAWS-injected Ccr2+/+ mice, processes that were ameliorated following the genetic inactivation of CCR2.
Collectively, our findings provide novel insights into the role of CCR2 in the pathogenesis of vasculitis as seen in KD and highlight novel therapeutic targets, specifically for individuals resistant to first-line treatments.
PMCID: PMC3519555  PMID: 23074996
CCR2; Coronary vasculitis; Treg; Treg/Th17 imbalance

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