Cardiac and Obstetric Outcomes Associated With Mitral Valve Prolapse.

Mitral valve prolapse (MVP) is the most common valvular heart disease in women of reproductive age. Whether MVP increases the likelihood of adverse outcomes in pregnancy is unknown. The study objective was to examine the cardiac and obstetric outcomes associated with MVP in pregnant women. This retrospective cohort study, using the Healthcare Cost and Utilization Project National Readmission Sample database between 2010 and 2017, identified all pregnant women with MVP using the International Classification of Disease, Ninth and Tenth Revisions codes. The maternal cardiac and obstetric outcomes in pregnant women diagnosed with MVP were compared with women without MVP using multivariable logistic and Cox proportional hazard regression models adjusted for baseline demographic characteristics. There were 23,000 pregnancy admissions with MVP with an overall incidence of 16.9 cases per 10,000 pregnancy admissions. Pregnant women with MVP were more likely to die during pregnancy (adjusted hazard ratio 5.13, 95% confidence interval [CI] 1.09 to 24.16), develop cardiac arrest (adjusted odds ratio [aOR] 4.44, 95% CI 1.04 to 18.89), arrhythmia (aOR 10.96, 95% CI 9.17 to 13.12), stroke (aOR 6.90, 95% CI 1.26 to 37.58), heart failure (aOR 5.81, 95% CI 3.84 to 8.79), or suffer a coronary artery dissection (aOR 25.22, 95% CI 3.42 to 186.07) compared with women without MVP. Pregnancies with MVP were also associated with increased risks of preterm delivery (aOR 1.21, 95% CI 1.02 to 1.44) and preeclampsia/hemolysis, elevated liver enzymes, and low platelets syndrome (aOR 1.22, 95% CI 1.05 to 1.41). In conclusion, MVP in pregnancy is associated with adverse maternal cardiac outcomes and higher obstetric risks.

Structural Equation Modeling of In silico Perturbations.

Gene expression is controlled by multiple regulators and their interactions. Data from genome-wide gene expression assays can be used to estimate molecular activities of regulators within a model organism and extrapolate them to biological processes in humans. This approach is valuable in studies to better understand complex human biological systems which may be involved in diseases and hence, have potential clinical relevance. In order to achieve this, it is necessary to infer gene interactions that are not directly observed (i.e. latent or hidden) by way of structural equation modeling (SEM) on the expression levels or activities of the downstream targets of regulator genes. Here we developed an R Shiny application, termed "Structural Equation Modeling of In silico Perturbations (SEMIPs)" to compute a two-sided t-statistic (T-score) from analysis of gene expression data, as a surrogate to gene activity in a given human specimen. SEMIPs can be used in either correlational studies between outcome variables of interest or subsequent model fitting on multiple variables. This application implements a 3-node SEM model that consists of two upstream regulators as input variables and one downstream reporter as an outcome variable to examine the significance of interactions among these variables. SEMIPs enables scientists to investigate gene interactions among three variables through computational and mathematical modeling (i.e. in silico). In a case study using SEMIPs, we have shown that putative direct downstream genes of the GATA Binding Protein 2 (GATA2) transcription factor are sufficient to infer its activities in silico for the conserved progesterone receptor (PGR)-GATA2-SRY-box transcription factor 17 (SOX17) genetic network in the human uterine endometrium.

Peptides and pseudopeptide ligands: a powerful toolbox for the affinity purification of current and next-generation biotherapeutics.

Following the consolidation of therapeutic proteins in the fight against cancer, autoimmune, and neurodegenerative diseases, recent advancements in biochemistry and biotechnology have introduced a host of next-generation biotherapeutics, such as CRISPR-Cas nucleases, stem and car-T cells, and viral vectors for gene therapy. With these drugs entering the clinical pipeline, a new challenge lies ahead: how to manufacture large quantities of high-purity biotherapeutics that meet the growing demand by clinics and biotech companies worldwide. The protein ligands employed by the industry are inadequate to confront this challenge: while featuring high binding affinity and selectivity, these ligands require laborious engineering and expensive manufacturing, are prone to biochemical degradation, and pose safety concerns related to their bacterial origin. Peptides and pseudopeptides make excellent candidates to form a new cohort of ligands for the purification of next-generation biotherapeutics. Peptide-based ligands feature excellent target biorecognition, low or no toxicity and immunogenicity, and can be manufactured affordably at large scale. This work presents a comprehensive and systematic review of the literature on peptide-based ligands and their use in the affinity purification of established and upcoming biological drugs. A comparative analysis is first presented on peptide engineering principles, the development of ligands targeting different biomolecular targets, and the promises and challenges connected to the industrial implementation of peptide ligands. The reviewed literature is organized in (i) conventional (α-)peptides targeting antibodies and other therapeutic proteins, gene therapy products, and therapeutic cells; (ii) cyclic peptides and pseudo-peptides for protein purification and capture of viral and bacterial pathogens; and (iii) the forefront of peptide mimetics, such as ß-/γ-peptides, peptoids, foldamers, and stimuli-responsive peptides for advanced processing of biologics.

Photoinduced reconfiguration to control the protein-binding affinity of azobenzene-cyclized peptides.

The impact of next-generation biorecognition elements (ligands) will be determined by the ability to remotely control their binding activity for a target biomolecule in complex environments. Compared to conventional mechanisms for regulating binding affinity (pH, ionic strength, or chaotropic agents), light provides higher accuracy and rapidity, and is particularly suited for labile targets. In this study, we demonstrate a general method to develop azobenzene-cyclized peptide ligands with light-controlled affinity for target proteins. Light triggers a cis/trans isomerization of the azobenzene, which results in a major structural rearrangement of the cyclic peptide from a non-binding to a binding configuration. Critical to this goal are the ability to achieve efficient photo-isomerization under low light dosage and the temporal stability of both cis and trans isomers. We demonstrated our method by designing photo-switchable peptides targeting vascular cell adhesion marker 1 (VCAM1), a cell marker implicated in stem cell function. Starting from a known VCAM1-binding linear peptide, an ensemble of azobenzene-cyclized variants with selective light-controlled binding were identified by combining in silico design with experimental characterization via spectroscopy and surface plasmon resonance. Variant cycloAZOB[G-VHAKQHRN-K] featured rapid, light-controlled binding of VCAM1 (KD,trans/KD,cis ∼ 130). Biotin-cycloAZOB[G-VHAKQHRN-K] was utilized to label brain microvascular endothelial cells (BMECs), showing co-localization with anti-VCAM1 antibodies in cis configuration and negligible binding in trans configuration.

Affibody-Binding Ligands.

While antibodies remain established therapeutic and diagnostic tools, other protein scaffolds are emerging as effective and safer alternatives. Affibodies in particular are a new class of small proteins marketed as bio-analytic reagents. They feature tailorable binding affinity, low immunogenicity, high tissue permeation, and high expression titer in bacterial hosts. This work presents the development of affibody-binding peptides to be utilized as ligands for their purification from bacterial lysates. Affibody-binding candidates were identified by screening a peptide library simultaneously against two model affibodies (anti-immunoglobulin G (IgG) and anti-albumin) with the aim of selecting peptides targeting the conserved domain of affibodies. An ensemble of homologous sequences identified from screening was synthesized on Toyopearl® resin and evaluated via binding studies to select sequences that afford high product binding and recovery. The affibody-peptide interaction was also evaluated by in silico docking, which corroborated the targeting of the conserved domain. Ligand IGKQRI was validated through purification of an anti-ErbB2 affibody from an Escherichia coli lysate. The values of binding capacity (~5 mg affibody per mL of resin), affinity (KD ~1 µM), recovery and purity (64-71% and 86-91%), and resin lifetime (100 cycles) demonstrate that IGKQRI can be employed as ligand in affibody purification processes.

Evaluation of a Clinical Pharmacist-Led Automated Dispensing Cabinet Stewardship Program at a Tertiary Academic Medical Center.

BACKGROUND: There is little guidance regarding the best methodology or frequency to optimize automated dispensing cabinets. Clinical pharmacists are in the unique position to make decisions regarding automated dispensing cabinet inventory to best serve their specific patient population. OBJECTIVE: The purpose of this evaluation was to determine if automated dispensing cabinet optimization by clinical pharmacists would affect the number of dispenses from central pharmacy, number of stockouts, and inventory cost. METHODS: A retrospective analysis was completed to evaluate the quantity of medications dispensed from a central pharmacy department over 2 separate 2-month periods, with optimization of automated dispensing cabinets occurring in between. The differences in quantity of medications dispensed and redispensed, as well as the number of stockouts and inventory cost on all automated dispensing cabinets, were compared pre- and postintervention. RESULTS: There were 1132 medication additions, 262 medication removals, and 167 medication par level adjustments. Medications dispensed from central pharmacy were decreased by 12% from the preintervention group to the postintervention group. The number of stockouts per cabinet per day also decreased from 0.75 to 0.61 in the pre- and postintervention groups, respectively. The inventory-at-par cost level was decreased by 15%. CONCLUSION AND RELEVANCE: Automated dispensing cabinet optimization by clinical pharmacists led to increased medication availability on inpatient units and decreased the number of dispenses from central pharmacy. Simple yet meaningful interventions can be taken to improve multiple medication distribution metrics simultaneously.

Preoperative Risk Stratification of Right Ventricular Function Utilizing Cardiac Magnetic Resonance Imaging Compared With Echocardiographic and Hemodynamic Parameters.

Accurate right ventricle functional analysis prior to mechanical circulatory support continues to be valuable for preoperative stratification of patients at risk for developing right ventricular (RV) failure. While cardiac magnetic resonance imaging (CMR) remains the gold standard, CMR is limited by availability and patient-specific contraindications. Further investigation of other imaging modalities would be beneficial as it may serve as a surrogate to identifying RV systolic dysfunction. A single-center, retrospective study including 29 patients with advanced heart failure was performed. All patients underwent ventricular functional analysis with both CMR and echocardiography, and 19 patients underwent right heart catheterization. Predictability with multimodal assessment of RV function was determined using logistic regression methods. Of the 29 participants, 10 had severe RV dysfunction. Tricuspid annular plane of systolic excursion was a modest predictor of RV dysfunction with odd ratio (OR) of 0.07 (0.01-0.72) and c-statistic of 0.79. Invasive hemodynamic measurement of cardiac index by thermodilution method was also predictive of RV dysfunction but failed to reach statistical significance (OR of 0.03, <0.001-1.28) with c-statistic of 0.83. The role of invasive hemodynamic data in predicting RV function compared with CMR should be further explored among patients with advanced heart failure.

Individualized feedback to change multiple gait deficits in chronic stroke.

BACKGROUND: Walking deficits in people post-stroke are often multiple and idiosyncratic in nature. Limited patient and therapist resources necessitate prioritization of deficits such that some may be left unaddressed. More efficient delivery of therapy may alleviate this challenge. Here, we look to determine the utility of a novel principal component-based visual feedback system that targets multiple, patient-specific features of gait in people post-stroke. METHODS: Ten individuals with stroke received two sessions of visual feedback to attain a walking goal. This goal consisted of bilateral knee and hip joint angles of a typical 'healthy' walking pattern. The feedback system uses principal component analysis (PCA) to algorithmically weight each of the input features so that participants received one stream of performance feedback. In the first session, participants had to explore different patterns to achieve the goal, and in the second session they were informed of the goal walking pattern. Ten healthy, age-matched individuals received the same paradigm, but with a hemiparetic goal (i.e. to produce the pattern of an exemplar stroke participant). This was to distinguish the extent to which performance limitations in stroke were due neurological injury or the PCA based visual feedback itself. RESULTS: Principal component-based visual feedback can differentially bias multiple features of walking toward a prescribed goal. On average, individuals with stroke typically improved performance via increased paretic knee and hip flexion, and did not perform better with explicit instruction. In contrast, healthy people performed better (i.e. could produce the desired exemplar stroke pattern) in both sessions, and were best with explicit instruction. Importantly, the feedback for stroke participants accommodated a heterogeneous set of walking deficits by individually weighting each feature based on baseline walking. CONCLUSIONS: People with and without stroke are able to use this novel visual feedback to train multiple, specific features of gait. Important for stroke, the PCA feedback allowed for targeting of patient-specific deficits. This feedback is flexible to any feature of walking in any plane of movement, thus providing a potential tool for therapists to simultaneously target multiple aberrant features of gait.

Providing low-dimensional feedback of a high-dimensional movement allows for improved performance of a skilled walking task.

Learning a skilled movement often requires changing multiple dimensions of movement in a coordinated manner. Serial training is one common approach to learning a new movement pattern, where each feature is learned in isolation from the others. Once one feature is learned, we move on to the next. However, when learning a complex movement pattern, serial training is not only laborious but can also be ineffective. Often, movement features are linked such that they cannot simply be added together as we progress through training. Thus, the ability to learn multiple features in parallel could make training faster and more effective. When using visual feedback as the tool for changing movement, however, such parallel training may increase the attentional load of training and impair performance. Here, we developed a novel visual feedback system that uses principal component analysis to weight four features of movement to create a simple one-dimensional 'summary' of performance. We used this feedback to teach healthy, young participants a modified walking pattern and compared their performance to those who received four concurrent streams of visual information to learn the same goal walking pattern. We demonstrated that those who used the principal component-based visual feedback improved their performance faster and to a greater extent compared to those who received concurrent feedback of all features. These results suggest that our novel principal component-based visual feedback provides a method for altering multiple features of movement toward a prescribed goal in an intuitive, low-dimensional manner.

Discovery and Evaluation of Peptide Ligands for Selective Adsorption and Release of Cas9 Nuclease on Solid Substrates.

The rapid expansion of CRISPR in biotechnology, medicine, and bioprocessing poses an urgent need for advanced manufacturing of Cas nucleases. The lack of Cas-targeting ligands, however, prevents the development of platform processes for purifying this class of molecules. This work represents the first effort at developing short synthetic Cas9-binding peptides and demonstrates their applicability as affinity ligands for the purification of a Cas nuclease. Candidate Cas9-targeting peptides were initially identified by screening a solid-phase peptide library against a model mixture of Streptococcus pyogenes Cas9 spiked in Escherichia coli cell lysate. An ensemble of homologous sequences was identified, conjugated on Toyopearl resin, and evaluated by Cas9 binding studies to identify sequences providing selective Cas9 capture and efficient release. In silico docking studies were also performed to evaluate the binding energy and site of the various peptides on Cas9. Notably, sequences GYYRYSEY and YYHRHGLQ were shown to target the RecII domain of Cas9, which is not involved in nuclease activity and was targeted as an ideal binding site. The peptide ligands were validated by purifying Cas9 from the E. coli lysate in dynamic conditions and through measurements of binding capacity and strength (Qmax and KD). The resulting values of Qmax = 4-5 mg Cas9 per mL of resin and KD ∼ 0.1-0.3 µM, product recovery (86-89%), and purity (91%-93%) indicate that both peptides, and YYHRHGLQ in particular, can serve as capture ligands in a platform purification process of Cas9.

Survey of confidence in use of stroke and bleeding risk calculators, knowledge of anticoagulants, and comfort with prescription of anticoagulation in challenging scenarios: SUPPORT-AF II study.

Half of patients with atrial fibrillation (AF) and elevated stroke risk do not receive anticoagulation (AC). Explanations for undertreatment may relate to provider lack of confidence with or knowledge of the CHA2DS2-VASc stroke calculator, unfamiliarity with direct oral anticoagulants (DOACs), or uncertainty about use of AC after bleeding events or other challenging patient scenarios. We surveyed cardiology and primary care providers (PCPs) within a large healthcare system to investigate prescriber knowledge, confidence, and comfort prescribing AC for AF in challenging scenarios. Of 112 providers invited, 70 (63%) completed our survey. Compared with non-responding providers, responding providers had fewer years in practice and more often worked in a university setting. Responding providers were moderately or very confident with use of CHA2DS2-VASc calculator (90%). Cardiology providers reported substantial knowledge about DOACs (72%) compared with PCPs (33%). Both provider groups reported reluctance prescribing AC when presented with challenging patient scenarios (% providers agreeing with AC): three falls over 6 months (36%), 2 weeks after resolved gastrointestinal bleed (21%), 4 weeks after intracranial bleeding (9%), in a patient consuming five alcoholic drinks per day (44%). All providers were moderately or very confident with using the CHA2DS2-VASc calculator, but only cardiology providers reported substantial knowledge about DOACs. Our providers were reluctant to prescribe AC after bleeding and in other common situations where use of AC may be appropriate. Education of PCPs about DOACs and development of guidelines to address challenging patient scenarios may improve AC prescription rates in patients with AF.

Affordable Microfluidic Bead-Sorting Platform for Automated Selection of Porous Particles Functionalized with Bioactive Compounds.

The ability to rapidly and accurately evaluate bioactive compounds immobilized on porous particles is crucial in the discovery of drugs, diagnostic reagents, ligands, and catalysts. Existing options for solid phase screening of bioactive compounds, while highly effective and well established, can be cost-prohibitive for proof-of-concept and early stage work, limiting its applicability and flexibility in new research areas. Here, we present a low-cost microfluidics-based platform enabling automated screening of small porous beads from solid-phase peptide libraries with high sensitivity and specificity, to identify leads with high binding affinity for a biological target. The integration of unbiased computer assisted image processing and analysis tools, provided the platform with the flexibility of sorting through beads with distinct fluorescence patterns. The customized design of the microfluidic device helped with handling beads with different diameters (~100-300 µm). As a microfluidic device, this portable novel platform can be integrated with a variety of analytical instruments to perform screening. In this study, the system utilizes fluorescence microscopy and unsupervised image analysis, and can operate at a sorting speed of up to 125 beads/hr (~3.5 times faster than a trained operator) providing >90% yield and >90% bead sorting accuracy. Notably, the device has proven successful in screening a model solid-phase peptide library by showing the ability to select beads carrying peptides binding a target protein (human IgG).

Effect of a Pharmacist-Driven Medication Management Intervention Among Older Adults in an Inpatient Setting.

BACKGROUND: Older adults have a seven times greater risk than younger adults of being hospitalized due to an adverse drug event. OBJECTIVE: The objective of this study was to compare the number of potentially inappropriate medications (PIMs) on admission to the number of PIMs on discharge following pharmacist intervention. PATIENTS AND METHODS: This was a prospective, single-center pilot study performed at a tertiary medical center. Eighty-two adults aged 65 years or older on five or more medications who were admitted to the general medicine floor between December 2016 and May 2017 were included in the analysis. Pharmacists completed a review of prior admission medications and identified PIMs. Recommendations for PIMs were communicated to the medical team and documented in the patient's electronic medical record. PIMs were measured by the use of validated screening tools and an assessment of patient-specific parameters. RESULTS: Fifty-two percent of our patients were taking at least one PIM. The average number of PIMs on admission was found to be 0.84 ± 1.12. Pharmacist intervention resulted in a statistically significant reduction to an average of 0.56 ± 0.91 PIMs (P < 0.01). The mean time to complete the medication therapy management (MTM) process was 49.39 ± 16.2 min per patient. CONCLUSION: While pharmacist-driven MTM significantly reduced PIMs in our study, the implementation of this model in the inpatient setting faces several challenges.

SUPPORT-AF: Piloting a Multi-Faceted, Electronic Medical Record-Based Intervention to Improve Prescription of Anticoagulation.

Background Only 50% of eligible atrial fibrillation ( AF ) patients receive anticoagulation ( AC ). Feasibility and effectiveness of electronic medical record (EMR)-based interventions to profile and raise provider AC percentage is poorly understood. The SUPPORT-AF (Supporting Use of AC Through Provider Profiling of Oral AC Therapy for AF) study aims to improve rates of adherence to AC guidelines by developing and delivering supportive tools based on the EMR to providers treating patients with AF. Methods and Results We emailed cardiologists and community-based primary care providers affiliated with our institution reports of their AC percentage relative to peers. We also sent an electronic medical record-based message to these providers the day before an appointment with an atrial fibrillation patient who was eligible but not receiving AC . The electronic medical record message asked the provider to discuss AC with the patient if he or she deemed it appropriate. To assess feasibility, we tracked provider review of our correspondence. We also tracked the change in AC for intervention providers relative to alternate primary care providers not receiving our intervention. We identified 3786, 1054, and 566 patients cared for by 49 cardiology providers, 90 community-based primary care providers, and 88 control providers, respectively. At baseline, the percentage of AC was 71.3%, 63.5%, and 58.3% for these 3 respective groups. Intervention providers reviewed our e-mails and electronic medical record messages 45% and 96% of the time, respectively. For providers responding, patient refusal was the most common reason for patients not being on AC (21%) followed by high bleeding risk (19%). At follow-up 10 weeks later, change in AC was no different for either cardiology or community-based primary care providers relative to controls (0.2% lower and 0.01% higher, respectively). Conclusions Our intervention profiling AC was feasible, but not sufficient to increase AC in our population.

Movement and perception recalibrate differently across multiple days of locomotor learning.

Learning a new movement through error-based adaptation leads to recalibration of movement and altered perception of that movement. Although presumed to be closely related, the relationship between adaptation-based motor and perceptual changes is not well understood. Here we investigated the changes in motor behavior and leg speed perception over 5 days of split-belt treadmill adaptation. We specifically wanted to know if changes in the perceptual domain would demonstrate savings-like behavior (i.e., less recalibration with more practice) and if these changes would parallel the savings observed in the motor domain. We found that the recalibration of leg speed perception decreased across days of training, indicating savings-like behavior in this domain. However, we observed that the magnitude of savings across days was different between motor and perceptual domains. These findings suggest a degree of independence between the motor and perceptual processes that occur with locomotor adaptation. NEW & NOTEWORTHY Error-based adaptation learning drives changes in movement and perception of movement. Are these changes across domains linked or simply coincidental? Here, we studied changes in movement and perception across 5 days of repeated locomotor adaptation. Savings-like behavior in the motor and perceptual domains developed with different magnitudes and over different timescales, leading us to conclude that motor and perceptual processes operate at least somewhat independently during locomotor adaptation.

Recent Trends in Oral Anticoagulant Use and Post-Discharge Complications Among Atrial Fibrillation Patients with Acute Myocardial Infarction.

BACKGROUND: Atrial fibrillation (AF) is a common complication of acute myocardial infarction (AMI).The CHA2DS2VAScand CHADS2risk scoresare used to identifypatients with AF at risk for strokeand to guide oral anticoagulants (OAC) use, including patients with AMI. However, the epidemiology of AF, further stratifiedaccording to patients' risk of stroke, has not been wellcharacterized among those hospitalized for AMI. METHODS: We examined trends in the frequency of AF, rates of discharge OAC use, and post-discharge outcomes among 6,627 residents of the Worcester, Massachusetts area who survived hospitalization for AMI at 11 medical centers between 1997 and 2011. RESULTS: A total of 1,050AMI patients had AF (16%) andthe majority (91%)had a CHA2DS2VAScscore >2.AF rates were highest among patients in the highest stroke risk group.In comparison to patients without AF, patients with AMI and AF in the highest stroke risk category had higher rates of post-discharge complications, including higher 30-day re-hospitalization [27 % vs. 17 %], 30-day post-discharge death [10 % vs. 5%], and 1-year post-discharge death [46 % vs. 18 %] (p < 0.001 for all). Notably, fewerthan half of guideline-eligible AF patientsreceived an OACprescription at discharge. Usage rates for other evidence-based therapiessuch as statins and beta-blockers,lagged in comparison to AMI patients free from AF. CONCLUSIONS: Our findings highlight the need to enhance efforts towards stroke prevention among AMI survivors with AF.

Accelerating locomotor savings in learning: compressing four training days to one.

Acquiring new movements requires the capacity of the nervous system to remember previously experienced motor patterns. The phenomenon of faster relearning after initial learning is termed "savings." Here we studied how savings of a novel walking pattern develops over several days of practice and how this process can be accelerated. We introduced participants to a split-belt treadmill adaptation paradigm for 30 min for 5 consecutive days. By training day 5, participants were able to produce near-perfect performance when switching between split and tied-belt environments. We found that this was due to their ability to shift specific elements of their stepping pattern to account for the split treadmill speeds from day to day. We also applied a state-space model to further characterize multiday locomotor savings. We then explored methods of achieving comparable savings with less total training time. We studied people training only on day 1, with either one extended split-belt exposure or alternating four times between split-belt and tied-belt conditions rapidly in succession. Both of these single-day training groups were tested again on day 5. Experiencing four abbreviated exposures on day 1 improved the performance on day 5 compared with one extended exposure on day 1. Moreover, this abbreviated group performed similarly to the group that trained for 4 consecutive days before testing on day 5, despite only having one-quarter of the total training time. These results demonstrate that we can leverage training structure to achieve a high degree of performance while minimizing training sessions. NEW & NOTEWORTHY Learning a new movement requires repetition. Here, we demonstrate how to more efficiently train an adapted walking pattern. By compressing split-belt treadmill training delivered over 4 days to four abbreviated bouts of training delivered on the first day of training, we were able to induce equivalent savings over a 5-day span. These results suggest that we can manipulate the delivery of training to most efficiently drive multiday learning of a novel walking pattern.

SYNTAX Score and Outcomes of Coronary Revascularization in Diabetic Patients.

PURPOSE OF REVIEW: This review describes the dynamic relationship between diabetes mellitus (DM) and coronary artery disease (CAD) with respect to different revascularization strategies and how angiographic tools such as the Synergy between PCI with Taxus and Cardiac Surgery (SYNTAX) score can supplement clinical decision-making. RECENT FINDINGS: The SYNTAX score characterizes the anatomical extent of CAD in terms of the number of lesions, functional importance, and complexity. Studies not limited to patients with DM suggest that percutaneous coronary intervention (PCI) is a reasonable alternative to coronary artery bypass grafting (CABG) in patients with low-medium SYNTAX scores, while patients with high SYNTAX scores should be revascularized with CABG if operable. Similar findings were also observed for diabetes patients with multivessel disease in retrospective pooled analysis. The SYNTAX II score combines anatomical and clinical risk to improve upon the decision regarding the optimal revascularization strategy. The SYNTAX II score can be applied to patients with DM. The SYNTAX scores provide guidance to clinicians faced with determining the optimal revascularization strategy in patients with DM and advanced CAD. Using a heart team approach, the information can be considered along with other factors that influence PCI or CABG risk.

Multifunctional PHPMA-Derived Polymer for Ratiometric pH Sensing, Fluorescence Imaging, and Magnetic Resonance Imaging.

In this paper, we report synthesis and characterization of a novel multimodality (MRI/fluorescence) probe for pH sensing and imaging. A multifunctional polymer was derived from poly(N-(2-hydroxypropyl)methacrylamide) (PHPMA) and integrated with a naphthalimide-based-ratiometric fluorescence probe and a gadolinium-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid complex (Gd-DOTA complex). The polymer was characterized using UV-vis absorption spectrophotometry, fluorescence spectrofluorophotometry, magnetic resonance imaging (MRI), and confocal microscopy for optical and MRI-based pH sensing and cellular imaging. In vitro labeling of macrophage J774 and esophageal CP-A cell lines shows the polymer's ability to be internalized in the cells. The transverse relaxation time (T2) of the polymer was observed to be pH-dependent, whereas the spin-lattice relaxation time (T1) was not. The pH probe in the polymer shows a strong fluorescence-based ratiometric pH response with emission window changes, exhibiting blue emission under acidic conditions and green emission under basic conditions, respectively. This study provides new materials with multimodalities for pH sensing and imaging.

ACR Appropriateness Criteria® Imaging of Deep Inferior Epigastric Arteries for Surgical Planning (Breast Reconstruction Surgery).

Breast cancer is the most common malignancy in women in the United States. Breast reconstruction surgery is a commonly used therapy for patients with breast cancer. The technique for the deep inferior epigastric perforator flap uses a preserved rectus muscle, which decreases donor site morbidity. Accurate identification and measurement of the perforator branches of the deep inferior epigastric artery is pivotal during pre-operative planning so that the surgeon can prioritize the best vessel to use and ultimately improve clinical outcome. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.