Citations

Transforming growth factor β (TGF-β) is critical for the development and maintenance of epithelial structures. Because receptor localization and trafficking affect the cellular and organismal response to TGF-β, the present study was designed to address how such homeostatic control is regulated. To that end, we identify a new role for the mammalian retromer complex in maintaining basolateral plasma membrane expression of the type II TGF-β receptor (TβRII). Retromer and TβRII associate in the presence or absence of TGF-β ligand. After retromer knockdown, although TβRII internalization and trafficking to a Rab5-positive compartment occur as in wild-type cells, receptor recycling is inhibited. This results in TβRII mislocalization from the basolateral to both the basolateral and apical plasma membranes independent of Golgi transit and the Rab11-positive apical recycling endosome. The data support a model in which, after initial basolateral TβRII delivery, steady-state polarized TβRII expression is maintained by retromer/TβRII binding and delivery to the common recycling endosome.

Atrial fibrillation ( AF ) is a cardiac arrhythmia associated with significant morbidity and mortality, affecting more than 3 million people in the United States and 1–2% of the population worldwide. Its estimated prevalence is expected to double within the next 50 years. During the past decade, there have been significant advances in the treatment of AF . Studies have demonstrated that a rate control strategy, with a target resting heart rate between 80 and 100 beats/minute, is recommended over rhythm control in the vast majority of patients. The CHA 2 DS 2 ≥ (congestive heart failure, hypertension, age ≥ 65 yrs, diabetes mellitus, stroke or transient ischemic attack, vascular disease, female gender) scoring system is a potentially useful stroke risk stratification tool that incorporates additional risk factors to the commonly used CHADS 2 (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, stroke transient ischemic attack) scoring tool. Similarly, a convenient scheme, termed HAS ‐ BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly), to assess bleeding risk has emerged that may be useful in select patients. Furthermore, new antithrombotic strategies have been developed as potential alternatives to warfarin, including dual‐antiplatelet therapy with clopidogrel plus aspirin and the development of new oral anticoagulants such as dabigatran, rivaroxaban, and apixaban. Vernakalant has emerged as another potential option for pharmacologic conversion of AF , whereas recent trials have better defined the role of dronedarone in the maintenance of sinus rhythm. Finally, catheter ablation represents another alternative to manage AF , whereas upstream therapy with inhibitors of the renin‐angiotensin‐aldosterone system, statins, and polyunsaturated fatty acids could potentially prevent the occurrence of AF . Despite substantial progress in the management of AF , significant uncertainty surrounds the optimal treatment of this condition.

Aberrant connectivity is implicated in many neurological and psychiatric disorders, including Alzheimer’s disease and schizophrenia. However, other than a few disease-associated candidate genes, we know little about the degree to which genetics play a role in the brain networks; we know even less about specific genes that influence brain connections. Twin and family-based studies can generate estimates of overall genetic influences on a trait, but genome-wide association scans (GWASs) can screen the genome for specific variants influencing the brain or risk for disease. To identify the heritability of various brain connections, we scanned healthy young adult twins with high-field, high-angular resolution diffusion MRI. We adapted GWASs to screen the brain’s connectivity pattern, allowing us to discover genetic variants that affect the human brain’s wiring. The association of connectivity with the SPON1 variant at rs2618516 on chromosome 11 (11p15.2) reached connectome-wide, genome-wide significance after stringent statistical corrections were enforced, and it was replicated in an independent subsample. rs2618516 was shown to affect brain structure in an elderly population with varying degrees of dementia. Older people who carried the connectivity variant had significantly milder clinical dementia scores and lower risk of Alzheimer’s disease. As a posthoc analysis, we conducted GWASs on several organizational and topological network measures derived from the matrices to discover variants in and around genes associated with autism ( MACROD2 ), development ( NEDD4 ), and mental retardation ( UBE2A ) significantly associated with connectivity. Connectome-wide, genome-wide screening offers substantial promise to discover genes affecting brain connectivity and risk for brain diseases.

Abstract Objectives Technology‐enhanced simulation is used frequently in emergency medicine ( EM ) training programs. Evidence for its effectiveness, however, remains unclear. The objective of this study was to evaluate the effectiveness of technology‐enhanced simulation for training in EM and identify instructional design features associated with improved outcomes by conducting a systematic review. Methods The authors systematically searched MEDLINE , EMBASE , CINAHL , ERIC , Psych INFO , Scopus, key journals, and previous review bibliographies through May 2011. Original research articles in any language were selected if they compared simulation to no intervention or another educational activity for the purposes of training EM health professionals (including student and practicing physicians, midlevel providers, nurses, and prehospital providers). Reviewers evaluated study quality and abstracted information on learners, instructional design (curricular integration, feedback, repetitive practice, mastery learning), and outcomes. Results From a collection of 10,903 articles, 85 eligible studies enrolling 6,099 EM learners were identified. Of these, 56 studies compared simulation to no intervention, 12 compared simulation with another form of instruction, and 19 compared two forms of simulation. Effect sizes were pooled using a random‐effects model. Heterogeneity among these studies was large (I 2 ≥ 50%). Among studies comparing simulation to no intervention, pooled effect sizes were large (range = 1.13 to 1.48) for knowledge, time, and skills and small to moderate for behaviors with patients (0.62) and patient effects (0.43; all p < 0.02 except patient effects p = 0.12). Among comparisons between simulation and other forms of instruction, the pooled effect sizes were small (≤0.33) for knowledge, time, and process skills (all p > 0.1). Qualitative comparisons of different simulation curricula are limited, although feedback, mastery learning, and higher fidelity were associated with improved learning outcomes. Conclusions Technology‐enhanced simulation for EM learners is associated with moderate or large favorable effects in comparison with no intervention and generally small and nonsignificant benefits in comparison with other instruction. Future research should investigate the features that lead to effective simulation‐based instructional design.

BACKGROUNDCross‐sectional data on inpatient glucose control in a large sample of US hospitals are now available, but little is known about changes in glycemic control over time in these institutions.OBJECTIVETo evaluate trends in glycemic control in US hospitals over 2 years.DESIGNRetrospective analysis.METHODSPoint‐of‐care blood glucose (POC‐BG) test results at 126 hospitals during January to December 2007 and January to December 2009 were extracted using the Remote Automated Laboratory System‐Plus (Medical Automation Systems, Charlottesville, VA), and patient‐day‐weighted mean glucose levels were compared.SETTING/PATIENTSHospitalized patients.RESULTSA total of 12,541,929 POC‐BG measurements from 1,010,705 patients were analyzed for 2007, and 10,659,418 POC‐BG measurements from 656,206 patients were analyzed for 2009. Patient‐day‐weighted mean POC‐BG in 2009 decreased by 5 mg/dL in the non‐intensive care unit (non‐ICU) data compared with that in 2007 (154 mg/dL vs 159 mg/dL, respectively; P < 0.001). However, POC‐BG values were clinically unchanged in intensive care unit (ICU) data from 2009 vs 2007 (167 mg/dL vs 166 mg/dL; P < 0.001). From 2007 to 2009, the proportion of patient‐day‐weighted mean POC‐BGs that were >180 mg/dL declined from 28% to 25% in non‐ICU patients (P < 0.001), but not in ICU. Decreases in patient‐day‐weighted mean POC‐BG values in non‐ICU patients were significant regardless of hospital size, type, and geographic region (all P < 0.001), but similar decreases were not found in ICU data.CONCLUSIONSIn this first analysis of glucose changes in US hospitals, improvements over 2 years occurred in non‐ICU patients. Ongoing analysis will determine whether this trend continues. Journal of Hospital Medicine 2013;8:121–125. © 2012 Society of Hospital Medicine

AbstractA plenary panel session at the 2012 Academic Emergency Medicine consensus conference “Education Research in Emergency Medicine: Opportunities, Challenges, and Strategies for Success” discussed barriers educators face in imagining, designing, and implementing studies to address educational challenges. This proceedings article presents a general approach to getting started in education research. Four examples of studies from the medical education literature that illustrate a distinct way to approach specific research questions are discussed. The study designs used are applicable to a variety of education research problems in emergency medicine (EM). Potential applications of studies are discussed, as well as effects and lessons learned.