Faculty Bibliography

PURPOSE:To determine medical students' study behaviors when preparing for the United States Medical Licensing Examination (USMLE) Step 1, and how these behaviors are associated with Step 1 scores when controlling for likely covariates. METHOD:The authors distributed a study-behaviors survey in 2014 and 2015 at their institution to two cohorts of medical students who had recently taken Step 1. Demographic and academic data were linked to responses. Descriptive statistics, bivariate correlations, and multiple linear regression analyses were performed. RESULTS:Of 332 medical students, 274 (82.5%) participated. Most students (n = 211; 77.0%) began studying for Step 1 during their preclinical curriculum, increasing their intensity during a protected study period during which they averaged 11.0 hours studying per day (standard deviation [SD] 2.1) over a period of 35.3 days (SD 6.2). Students used numerous third-party resources, including reading an exam-specific 700-page review book on average 2.1 times (SD 0.8) and completing an average of 3,597 practice multiple-choice questions (SD 1,611). Initiating study prior to the designated study period, increased review book usage, and attempting more practice questions were all associated with higher Step 1 scores, even when controlling for Medical College Admission Test scores, preclinical exam performance, and self-identified score goal (adjusted R = 0.56, P < .001). CONCLUSIONS:Medical students at one public institution engaged in a self-directed, "parallel" Step 1 curriculum using third-party study resources. Several study behaviors were associated with improved USMLE Step 1 performance, informing both institutional- and student-directed preparation for this high-stakes exam.

Background: Polyphenols offer high antioxidant potential that may protect against chronic diseases. Epidemiologic evidence documenting their influence on body composition and obesity risk is limited, particularly among Hispanics/Latinos who are disproportionately prone to obesity. Objectives: The aims of this study were to evaluate cross-sectional associations of urinary polyphenols with body mass index (BMI) and body fat percentage (%BF) in a diverse Hispanic/Latino population and to assess the reliability of polyphenol measurements. Methods: Participants were 442 adults from the Study of Latinos/Nutrition and Physical Activity Assessment Study (SOLNAS) aged 18-74 y. Doubly labeled water was used as an objective recovery biomarker of energy. Polyphenol excretion from 24-h urine samples was assessed. Measures were repeated in a subsample (n = 90) to provide a reliability measure. Anthropometric measures were obtained by trained personnel, and %BF was measured by ¹⁸O dilution. Linear regression models were used to evaluate multivariable associations between body composition and polyphenols. Spearman correlation coefficients between BMI and %BF with polyphenols and intraclass correlation coefficients (ICCs) between polyphenol measures were computed. Results: A weak correlation was observed for resveratrol and %BF (r = -0.11, P = 0.02). In multivariable-adjusted regression models, weak inverse associations were observed for resveratrol and urolithin A with %BF [β ± SE: -0.010 ± 0.004 (P = 0.007) and -0.004 ± 0.002 (P = 0.03), respectively]. For every 50% increase in these urinary polyphenols, there was a 1% and 0.4% decrease in %BF. Urolithin A was inversely associated with BMI (β ± SE: -0.004 ± 0.002; P = 0.02) and with 5% lower odds of obesity in models not adjusted for total energy expenditure (TEE; OR: 0.95; 95% CI: 0.91, 0.99; P = 0.02). For every 50% increase in urolithin A, there was a 0.4-unit decrease in BMI. Associations were attenuated after adjustment for TEE. Reliability study findings were indicative of weak to moderate correlations (ICCs: 0.11-0.65), representing a degree of within-person variation in polyphenol biomarkers. Conclusions: Although associations were weak, resveratrol and urolithin A were inversely associated with obesity. Repeated polyphenol urine measures could clarify their long-term impact on body adiposity.

Introduction/Rational A 72 year old male with history of amyloid angiopathy and cerebral hemorrhages sustained an acute left temporal parietal intraparenchymal hemorrhage. He was noted to have impairments in visual perception, memory, language and balance. The patient was diagnosed with Balint's Syndrome which includes a trio of symptoms - inability to perceive the visual field as a whole (simultanagnosia), difficulty in fixating the eyes (oculomotor apraxia), and inability to move the hand to a specific object by using vision (optic ataxia). The patient required acute inpatient rehabilitation to address this unique set of impairments. Method/Approach An interdisciplinary approach was utilized focusing on taskbased training to improve his cognitive, functional and physical functioning. The patient benefited from errorless learning techniques, a low stimulation environment, and proprioceptive input to improve balance and coordination. Objective testing with the O-LOG, FIM, Berg Balance Test, and a specialized protocol for spaced retrieval of orientation information were utilized in order to track the patient's rehabilitation progress. Results/Effects The patient demonstrated improvement in orientation (8/30 to 20/30 on O-LOG), balance (0/56 to 17/56 on Berg Balance Test), basic communication skills, and self-care activities over four weeks. This case report demonstrates a unique rehabilitation approach to Balint's Syndrome, whereby established objective scales were incorporated to measure the patient's functional improvements over time. Limited research suggests rehabilitation training should be focused on the improvement of visual scanning, the development of visually guidedmanualmovements, and integration of visual elements. This case report agrees with these findings and supports an interdisciplinary approach to address patients with complex functional impairments. Conclusions/Limitations This case report supports published reports of treating Balint's syndrome with an interdisciplinary approach. However, more research is needed to validate an effective clinical approach for this distinctive syndrome

The emergence of Klebsiella pneumoniae carbapenemases (KPCs), β-lactamases that inactivate "last-line" antibiotics such as imipenem, represents a major challenge to contemporary antibiotic therapies. The combination of ceftazidime (CAZ) and avibactam (AVI), a potent β-lactamase inhibitor, represents an attempt to overcome this formidable threat and to restore the efficacy of the antibiotic against Gram-negative bacteria bearing KPCs. CAZ-AVI-resistant clinical strains expressing KPC variants with substitutions in the Ω-loop are emerging. We engineered 19 KPC-2 variants bearing targeted mutations at amino acid residue Ambler position 179 in Escherichia coli and identified a unique antibiotic resistance phenotype. We focus particularly on the CAZ-AVI resistance of the clinically relevant Asp179Asn variant. Although this variant demonstrated less hydrolytic activity, we demonstrated that there was a prolonged period during which an acyl-enzyme intermediate was present. Using mass spectrometry and transient kinetic analysis, we demonstrated that Asp179Asn "traps" β-lactams, preferentially binding β-lactams longer than AVI owing to a decreased rate of deacylation. Molecular dynamics simulations predict that (i) the Asp179Asn variant confers more flexibility to the Ω-loop and expands the active site significantly; (ii) the catalytic nucleophile, S70, is shifted more than 1.5 Å and rotated more than 90°, altering the hydrogen bond networks; and (iii) E166 is displaced by 2 Å when complexed with ceftazidime. These analyses explain the increased hydrolytic profile of KPC-2 and suggest that the Asp179Asn substitution results in an alternative complex mechanism leading to CAZ-AVI resistance. The future design of novel β-lactams and β-lactamase inhibitors must consider the mechanistic basis of resistance of this and other threatening carbapenemases.IMPORTANCE Antibiotic resistance is emerging at unprecedented rates and threatens to reach crisis levels. One key mechanism of resistance is the breakdown of β-lactam antibiotics by β-lactamase enzymes. KPC-2 is a β-lactamase that inactivates carbapenems and β-lactamase inhibitors (e.g., clavulanate) and is prevalent around the world, including in the United States. Resistance to the new antibiotic ceftazidime-avibactam, which was designed to overcome KPC resistance, had already emerged within a year. Using protein engineering, we uncovered a mechanism by which resistance to this new drug emerges, which could arm scientists with the ability to forestall such resistance to future drugs.

Early results of a prospective phase 2 clinical trial of carfilzomib, lenalidomide, and dexamethasone followed by lenalidomide maintenance in high-risk smoldering myeloma showed promising results that were previously published. Here, we provide novel insights into the genetic landscape of high-risk smoldering myeloma and information on sustained minimal residual disease (MRD) negativity with an expanded cohort of patients. Eighteen patients with high-risk smoldering myeloma were enrolled between 29 May 2012, and 14 January 2014. We included patients with newly diagnosed multiple myeloma enrolled in a parallel trial who received the same therapy (reference group). The overall response rate was 100%. With median potential follow-up of 43.3 months, 10 (63%) remain in MRD negativity, and the estimated 4-year progression-free and overall survival rates are 71% and 100%, respectively. Importantly, we report differences in mutational patterns in patients with high-risk smoldering myeloma and newly diagnosed multiple myeloma, reflected in a lower frequency of mutations in significant myeloma genes (6.6% vs 45%) andNFKBpathway genes (6.6% vs 25%). Treatment with carfilzomib, lenalidomide, and dexamethasone followed by lenalidomide maintenance was associated with a 100% response rate and 63% MRD negativity with a safety profile consistent with previous reports for this regimen. This study had a small numbers of participants, but there seemed to be important differences in the genetic landscape of patients with high-risk smoldering myeloma and those with newly diagnosed multiple myeloma, suggestive of a more treatment-responsive biology in early disease.