Incidental Lung Nodules on Cross-sectional Imaging: Current Reporting and Management.

Pulmonary nodules are the most common incidental finding in the chest, particularly on computed tomographs that include a portion or all of the chest, and may be encountered more frequently with increasing utilization of cross-sectional imaging. Established guidelines address the reporting and management of incidental pulmonary nodules, both solid and subsolid, synthesizing nodule and patient features to distinguish benign nodules from those of potential clinical consequence. Standard nodule assessment is essential for the accurate reporting of nodule size, attenuation, and morphology, all features with varying risk implications and thus management recommendations.

ACL injury and reconstruction affect control of ground reaction forces produced during a novel task that simulates cutting movements.

After anterior cruciate ligament (ACL) injury and reconstruction, biomechanical and neuromuscular control deficits persist and 25% of those who have experienced an ACL injury will experience a second ACL rupture in the first year after returning to sports. There remains a need for improved rehabilitation and the ability to detect an individual's risk of secondary ACL rupture. Nonlinear analysis metrics, such as the largest Lyapunov exponent (LyE) can provide new biomechanical insight in this population by identifying how movement patterns evolve over time. The purpose of this study was to determine how ACL injury, ACL reconstruction (ACLR), and participation in high-performance athletics affect control strategies, evaluated through nonlinear analysis, produced during a novel task that simulates forces generated during cutting movements. Uninjured recreational athletes, those with ACL injury who have not undergone reconstruction (ACLD [ACL deficient]), those who have undergone ACL reconstruction, and high-performance athletes completed a task that simulates cutting forces. The LyE calculated from forces generated during this novel task was greater (ie, force control was diminished) in the involved limb of ACLD and ACLR groups when compared with healthy uninjured controls and high-performance athletes. These data suggest that those who have experienced an ACL injury and subsequent reconstructive surgery exhibit poor force control when compared with both uninjured controls and high-performance athletes. Clinical significance: significantly larger LyE values after ACL injury and reconstruction when compared with healthy athletes suggest a continuing deficit in force control not addressed by current rehabilitation protocols and evaluation metrics that could contribute to secondary ACL rupture.

A Novel and Safe Approach to Simulate Cutting Movements Using Ground Reaction Forces.

Control of shear ground reaction forces (sGRF) is important in performing running and cutting tasks as poor sGRF control has implications for those with knee injuries, such as anterior cruciate ligament (ACL) ruptures. The goal of this study was to develop a novel and safe task to evaluate control or accurate modulation of shear ground reaction forces related to those generated during cutting. Our approach utilized a force control task using real-time visual feedback of a subject's force production and evaluated control capabilities through accuracy and divergence measurements. Ten healthy recreational athletes completed the force control task while force control via accuracy measures and divergence calculations was investigated. Participants were able to accurately control sGRF in multiple directions based on error measurements. Forces generated during the task were equal to or greater than those measured during a number of functional activities. We found no significant difference in the divergence of the force profiles using the Lyapunov Exponent of the sGRF trajectories. Participants using our approach produced high accuracy and low divergence force profiles and functional force magnitudes. Moving forward, we will utilize this task in at-risk populations who are unable to complete a cutting maneuver in early stages of rehabilitation, such as ACL deficient and newly reconstructed individuals, allowing insight into force control not obtainable otherwise.

The study to understand the genetics of the acute response to metformin and glipizide in humans (SUGAR-MGH): design of a pharmacogenetic resource for type 2 diabetes.

OBJECTIVE: Genome-wide association studies have uncovered a large number of genetic variants associated with type 2 diabetes or related phenotypes. In many cases the causal gene or polymorphism has not been identified, and its impact on response to anti-hyperglycemic medications is unknown. The Study to Understand the Genetics of the Acute Response to Metformin and Glipizide in Humans (SUGAR-MGH, NCT01762046) is a novel resource of genetic and biochemical data following glipizide and metformin administration. We describe recruitment, enrollment, and phenotyping procedures and preliminary results for the first 668 of our planned 1,000 participants enriched for individuals at risk of requiring anti-diabetic therapy in the future. METHODS: All individuals are challenged with 5 mg glipizide × 1; twice daily 500 mg metformin × 2 days; and 75-g oral glucose tolerance test following metformin. Genetic variants associated with glycemic traits and blood glucose, insulin, and other hormones at baseline and following each intervention are measured. RESULTS: Approximately 50% of the cohort is female and 30% belong to an ethnic minority group. Following glipizide administration, peak insulin occurred at 60 minutes and trough glucose at 120 minutes. Thirty percent of participants experienced non-severe symptomatic hypoglycemia and required rescue with oral glucose. Following metformin administration, fasting glucose and insulin were reduced. Common genetic variants were associated with fasting glucose levels. CONCLUSIONS: SUGAR-MGH represents a viable pharmacogenetic resource which, when completed, will serve to characterize genetic influences on pharmacological perturbations, and help establish the functional relevance of newly discovered genetic loci to therapy of type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT01762046.

Genotypic-phenotypic discrepancies between antibiotic resistance characteristics of Escherichia coli isolates from calves in management settings with high and low antibiotic use.

We hypothesized that bacterial populations growing in the absence of antibiotics will accumulate more resistance gene mutations than bacterial populations growing in the presence of antibiotics. If this is so, the prevalence of dysfunctional resistance genes (resistance pseudogenes) could provide a measure of the level of antibiotic exposure present in a given environment. As a proof-of-concept test, we assayed field strains of Escherichia coli for their resistance genotypes using a resistance gene microarray and further characterized isolates that had resistance phenotype-genotype discrepancies. We found a small but significant association between the prevalence of isolates with resistance pseudogenes and the lower antibiotic use environment of a beef cow-calf operation versus a higher antibiotic use dairy calf ranch (Fisher's exact test, P = 0.044). Other significant findings include a very strong association between the dairy calf ranch isolates and phenotypes unexplained by well-known resistance genes (Fisher's exact test, P < 0.0001). Two novel resistance genes were discovered in E. coli isolates from the dairy calf ranch, one associated with resistance to aminoglycosides and one associated with resistance to trimethoprim. In addition, isolates resistant to expanded-spectrum cephalosporins but negative for bla(CMY-2) had mutations in the promoter regions of the chromosomal E. coli ampC gene consistent with reported overexpression of native AmpC beta-lactamase. Similar mutations in hospital E. coli isolates have been reported worldwide. Prevalence or rates of E. coli ampC promoter mutations may be used as a marker for high expanded-spectrum cephalosporin use environments.