EMR documentation of physician–patient communication following genomic counseling for actionable complex disease and pharmacogenomic results

Genomic risk information for potentially actionable complex diseases and pharmacogenomics communicated through genomic counseling (GC) may motivate physicians and patients to take preventive actions. The Ohio State University‐Coriell Personalized Medicine Collaborative is a randomized trial to measure the effects of in‐person GC on chronic disease patients provided with multiplex results. Nine personalized genomic risk reports were provided to patients through a web portal, and to physicians via electronic medical record (EMR). Active arm participants (98, 39% female) received GC within 1 month of report viewing; control arm subjects (101, 54% female) could access counseling 3‐months post‐report viewing. We examined whether GC affected documentation of physician–patient communication by reviewing the first clinical note following the patient's GC visit or report upload to the EMR. Multivariable logistic regression modeling estimated the independent effect of GC on physician–patient communication, as intention to treat (ITT) and per protocol (PP), adjusted for physician educational intervention. Counselees in the active arm had more physician–patient communications than control subjects [ITT, odds ratio (OR): 3.76 (95% confidence interval (CI): 1.38–10.22, p < 0.0094); PP, OR: 5.53 (95% CI: 2.20–13.90, p = 0.0017). In conclusion, GC appreciably affected physician–patient communication following receipt of potentially actionable genomic risk information.     

Neodymium-decorated graphene oxide as a corrosion barrier layer on Ti6Al4V alloy in acidic medium

Ti6Al4V alloy is light weight and is used in construction, oil industries and airbus, automobile, and bio implant materials. The native oxide layers of the alloy are not stable at high temperatures and strong mineral acid environments. The conventional epoxy-based layers are porous and the alloy finally fails in the harsh environment in the long term. Therefore, the carbon-based functional materials are being proposed as coating materials to overcome the alloy degradation. In the present contribution, we have used the neodymium-decorated graphene oxide as the corrosion inhibiting barrier for the Ti6Al4V alloy. As a novelty, we found that the few-layer graphene decorated with neodymium acts as a self-cleaning coating. The Nd-decorated graphene oxide were studied by XRD, TEM, FESEM, FTIR, UV, and Raman spectroscopy. The corrosion inhibition efficiency was studied by electrochemical methods.

Neodymium-decorated graphene oxide is chemisorbed by non-bonding electrons on Ti6Al4V surface increasing the corrosion inhibition in acidic media.     

Memory-specific temporal profiles of gene expression in the hippocampus

Many experiments in the past have demonstrated the requirement of de novo gene expression during the long-term retention of learning and memory. Although previous studies implicated individual genes or genetic pathways in learning and memory, they did not uncover the collective behaviors or patterns of the genes. We have used genome-scale screening to analyze gene expression during spatial learning of rats in the Morris water maze. Our results show distinct temporal gene expression profiles associated with learning and memory. Exogenous administration of one peptide whose sustained increase during memory retention was implicated by microarray analysis, fibroblast growth factor (FGF)-18, improved spatial learning behavior, suggesting that pharmacological modulation of pathways and targets identified may allow new therapeutic approaches for improving learning and memory. Results of this study also suggest that while learning and physical activity involve common groups of genes, the behavior of learning and memory emerges from unique patterns of gene expression across time.     

Diffusion tensor imaging of forearm nerves in humans

Purpose:

To implement a diffusion tensor imaging (DTI) protocol for visualization of peripheral nerves in human forearm.

Materials and Methods:

This Health Insurance Portability and Accountability Act (HIPAA)‐compliant study was approved by our Institutional Review Board and written informed consent was obtained from 10 healthy participants. T₁‐ and T₂‐weighted turbo spin echo with fat saturation, short tau inversion recovery (STIR), and DTI sequences with 21 diffusion‐encoding directions were implemented to acquire images of the forearm nerves with an 8 channel knee coil on a 3T MRI scanner. Identification of the nerves was based on T₁‐weighted, T₂‐weighted, STIR, and DTI‐derived fractional anisotropy (FA) images. Maps of the DTI‐derived indices, FA, mean diffusivity (MD), longitudinal diffusivity (λ_//), and radial diffusivity (λ_?) along the length of the nerves were generated.

Results:

DTI‐derived maps delineated the forearm nerves more clearly than images acquired with other sequences. Only ulnar and median nerves were clearly visualized on the DTI‐derived FA maps. No significant differences were observed between the left and right forearms in any of the DTI‐derived measures. Significant variation in the DTI measures was observed along the length of the nerve. Significant differences in the DTI measures were also observed between the median and ulnar nerves.

Conclusion:

DTI is superior in visualizing the median and ulnar nerves in the human forearm. The normative data could potentially help distinguish normal from diseased nerves. J. Magn. Reson. Imaging 2012;36:920–927. © 2012 Wiley Periodicals, Inc.

     

Quantifying the breadth of antibiotic exposure in sepsis and suspected infection using spectrum scores

A retrospective cohort study. Studies to quantify the breadth of antibiotic exposure across populations remain limited. Therefore, we applied a validated method to describe the breadth of antimicrobial coverage in a multicenter cohort of patients with suspected infection and sepsis. We conducted a retrospective cohort study across 21 hospitals within an integrated healthcare delivery system of patients admitted to the hospital through the ED with suspected infection or sepsis and receiving antibiotics during hospitalization from January 1, 2012, to December 31, 2017. We quantified the breadth of antimicrobial coverage using the Spectrum Score, a numerical score from 0 to 64, in patients with suspected infection and sepsis using electronic health record data. Of 364,506 hospital admissions through the emergency department, we identified 159,004 (43.6%) with suspected infection and 205,502 (56.4%) with sepsis. Inpatient mortality was higher among those with sepsis compared to those with suspected infection (8.4% vs 1.2%; P < .001). Patients with sepsis had higher median global Spectrum Scores (43.8 [interquartile range IQR 32.0–49.5] vs 43.5 [IQR 26.8–47.2]; P < .001) and additive Spectrum Scores (114.0 [IQR 57.0–204.5] vs 87.5 [IQR 45.0–144.8]; P < .001) compared to those with suspected infection. Increased Spectrum Scores were associated with inpatient mortality, even after covariate adjustments (adjusted odds ratio per 10-point increase in Spectrum Score 1.31; 95%CI 1.29–1.33). Spectrum Scores quantify the variability in antibiotic breadth among individual patients, between suspected infection and sepsis populations, over the course of hospitalization, and across infection sources. They may play a key role in quantifying the variation in antibiotic prescribing in patients with suspected infection and sepsis.     

Field dependent transverse relaxation rate increase may be a specific measure of tissue iron stores

The degree to which MRI magnet field strength affects measured transverse relaxation rates (R₂) defines a measure termed the field dependent R₂ increase (FDRI). We report here the results of in vivo and in vitro experiments that were conducted to evaluate whether FDRI is a potentially useful measure of tissue iron stores. T₂ relaxation times were obtained using two clinical MRI instruments operating at 0.5 and 1.5 Tesla, and relaxation rates (R₂) were calculated as the reciprocal of T₂. The in vivo experiment measured R₂ in human brain frontal white matter, caudate nucleus, putamen, and globus pallidus. The FDRI was very highly correlated with published brain iron levels for the four regions examined. The in vitro experiment measured R₂ in agarose gel-based phantoms containing physiologic forms and amounts proteins involved in iron storage and transport (ferritin, apoferritin, transferrin, and apotransferrin). Significant field dependence was observed only for the ferritin phantoms. The differences in the R₂ values obtained at the two field strengths were striking, and were proportional to the ferritin levels of the phantoms. These studies suggest that FDRI may be a specific measure of tissue ferritin. The quantitative significance of the results to imaging and possible applications to the clinical investigation of pathologic states are discussed.     

Two transforming C-RAF germ-line mutations identified in patients with therapy-related acute myeloid leukemia

Mutations leading to activation of the RAF-mitogen-activated protein kinase/extracellular signal-regulated (ERK) kinase (MEK)-ERK pathway are key events in the pathogenesis of human malignancies. In a screen of 82 acute myeloid leukemia (AML) samples, 45 (55%) showed activated ERK and thus were further analyzed for mutations in B-RAF and C-RAF. Two C-RAF germ-line mutations, S427G and I448V, were identified in patients with therapy-related AML in the absence of alterations in RAS and FLT3. Both exchanges were located within the kinase domain of C-RAF. In vitro and in vivo kinase assays revealed significantly increased activity for (S427G)C-RAF but not for (I448V)C-RAF. The involvement of the S427G C-RAF mutation in constitutive activation of ERK was further confirmed through demonstration of activating phosphorylations on C-RAF, MEK, and ERK in neoplastic cells, but not in nonneoplastic cells. Transformation and survival assays showed oncogenic and antiapoptotic properties for both mutations. Screening healthy individuals revealed a <1/400 frequency of these mutations and, in the case of I448V, inheritance was observed over three generations with another mutation carrier suffering from cancer. Taken together, these data are the first to relate C-RAF mutations to human malignancies. As both mutations are of germ-line origin, they might constitute a novel tumor-predisposing factor.