Technical feasibility of uro-dynamic MRI study of voiding biomechanics: a pilot study.

INTRODUCTION: Dynamic volumetric MRI was used to non-invasively assess voiding biomechanics in a healthy male volunteer. METHODS: Using 3D Differential Subsampling with Cartesian Ordering (DISCO) Flex acquisition sequence, volumetric bladder images were obtained throughout the voiding effort. These were subsequently segmented using MIMICS. Segmented anatomical volumes were used to quantify total voided volume, post-void residual, volumetric displacement of urine over time, bladder neck angle, sphericity index, and prostatic urethral angle through the voiding effort. RESULTS: Bladder sphericity index correlated positively with flow rate. The greatest degree of bladder neck funneling correlated with the maximum urine flow rate. There was straightening of the prostatic urethral angle during voiding that also correlated positively with urine flow. CONCLUSION: This pilot study confirms the potential of dynamic MRI to provide non-invasive assessment of lower urinary tract anatomy and biomechanics during voiding.

Graphene-Enhanced Ion Transport in Dual-Conducting Composite Films of Polyacetylene and an Imidazolium Iodide Ionic Liquid.

Dual-conducting polymer films were synthesized by dispersing graphene in an aqueous solution of poly(vinyl alcohol) and 1-propyl-3-methylimidazolium iodide ([C3mim]I) ionic liquid and thermally converting the poly(vinyl alcohol) to polyene in the presence of hydroiodic acid catalyst. The electrical and mechanical properties of the resulting free-standing films of the nanocomposite, containing different concentrations of graphene, were analyzed using electrochemical impedance spectroscopy (EIS) and dynamic mechanical analysis (DMA), respectively. Nyquist plots (imaginary vs real components of the frequency-dependent impedance) showed two characteristic arcs representing the composite's electronic and ionic conduction pathways. The conductivity values corresponding to both charge transport mechanisms increased with temperature and the graphene concentration. The enhancement in electronic conductivity is expected because of graphene's high electron mobility. Interestingly, ionic conductivity also showed a significant increase with graphene concentration, approximately triple the extent of the rise in the electronic conductivity, even though the loss and storage moduli of the films increased. (Generally, a higher modulus results in lower ionic conductivities in ionic gels.) Molecular dynamics simulations of the three-component system provided some insights into this unusual behavior. Mean square displacement data showed that the diffusion of the iodide anions was relatively isotropic. The iodide diffusion coefficient was higher in a blend with 5 vol % graphene than in blends with 3 vol % graphene or no graphene. The improvement is attributed to the interfacial effects of the graphene on the free volume of the blend. Furthermore, an exclusion of the iodide ions from the vicinity of graphene was observed in the radial distribution function analysis. The increase in the effective concentration of iodide due to this exclusion and the increase in its diffusion coefficient because of the excess free volume are the primary reasons for the observed enhancement in ionic conductivity by adding graphene.

Effect of Metabolic Syndrome on Anatomy and Function of the Lower Urinary Tract Assessed on MRI.

OBJECTIVE: To investigate the relationship between metabolic syndrome (MetS) and lower urinary tract symptoms (LUTS) with functional and anatomic changes of the lower urinary tract with MRI. MATERIALS AND METHODS: The bladder and prostate of 95 subjects (56M, 39F) were segmented on T2-weighted pelvic MRI using Materialize Mimics 3D software. Bladder wall volume (BWV), post-void residual (PVR) and prostate volume (PV) were quantified from the 3D renderings. LUTS were quantified using validated questionnaires administered at the time of MRI. Wilcoxin rank sum, win ratio and chi-square tests were used to correlate symptom scores, BWV, PVR and PV in patients 1) without vs with MetS, 2) with mild (IPSS or UDI-6: 0-7) vs moderate-severe (IPSS: 8-35 or UDI-6: ≥8) and 3) normal vs enlarged prostates (>40cm3). Multivariate linear regression was used to determine predictors for BWV, PVR and PV. RESULTS: Men with MetS had increased BWV (66.8 vs 51.1cm3, P = .003), higher PVR (69.1 vs 50.5cc, P= .05) and increased PV (67.2 vs 40.1cm3, P= .01). Women without and with MetS had similar BWV, PVR and LUTS (P= .3-.78). There was no difference in prevalence of MetS, BWV, PVR or PV in men or women with mild vs moderate-severe LUTS (P = .26-.97). Men with enlarged prostates were more likely to have MetS (P = .003). There was no difference in BWV, PVR and LUTS for men with normal vs enlarged prostates (P= .44-.94). In men, BWV was highly correlated with MetS (P = .005) on regression analysis. CONCLUSION: MetS leads to detrusor hypertrophy and may contribute to impaired bladder function, likely related to the effect on the prostate.

Assessment of sex differences in ventricular-vascular coupling of left ventricular and aortic flow derived from 4D flow MRI in healthy, young adults.

To gain further insight into male-female differences in cardiovascular conditions it is important to understand sex differences in healthy populations. A previous study from our group of 39 healthy young volunteers (20-35 years) paradoxically found that men had greater left ventricular (LV) kinetic energy (KE) but women had greater LV vorticity. We reanalyzed cardiac four-dimensional flow MRI data from 20 of the original subjects (10 male and 10 female) to quantify aortic flow in addition to LV flow. The combination of LV and aortic flow parameters were then used to calculate ventricular vascular coupling of KE and vorticity. The sex difference found in LV flow were not found in aortic flow and the ventricular-vascular coupling of LV-to-aortic flow was similar between men and women. Dimensional analysis to account for differences in cardiac output and ventricular volume explained the differences found in LV flow. The analysis methods and results of this study may be of further use in understanding ventricular vascular coupling of transported flow variables in healthy sex differences, healthy aging, and various cardiovascular conditions.

Stent interventions for pulmonary artery stenosis improve bi-ventricular flow efficiency in a swine model.

BACKGROUND: Branch pulmonary artery (PA) stenosis (PAS) commonly occurs in patients with congenital heart disease (CHD). Prior studies have documented technical success and clinical outcomes of PA stent interventions for PAS but the impact of PA stent interventions on ventricular function is unknown. The objective of this study was to utilize 4D flow cardiovascular magnetic resonance (CMR) to better understand the impact of PAS and PA stenting on ventricular contraction and ventricular flow in a swine model of unilateral branch PA stenosis. METHODS: 18 swine (4 sham, 4 untreated left PAS, 10 PAS stent intervention) underwent right heart catheterization and CMR at 20 weeks age (55 kg). CMR included ventricular strain analysis and 4D flow CMR. RESULTS: 4D flow CMR measured inefficient right ventricular (RV) and left ventricular (LV) flow patterns in the PAS group (RV non-dimensional (n.d.) vorticity: sham 82 ± 47, PAS 120 ± 47; LV n.d. vorticity: sham 57 ± 5, PAS 78 ± 15 p < 0.01) despite the PAS group having normal heart rate, ejection fraction and end-diastolic volume. The intervention group demonstrated increased ejection fraction that resulted in more efficient ventricular flow compared to untreated PAS (RV n.d. vorticity: 59 ± 12 p < 0.01; LV n.d. vorticity: 41 ± 7 p < 0.001). CONCLUSION: These results describe previously unknown consequences of PAS on ventricular function in an animal model of unilateral PA stenosis and show that PA stent interventions improve ventricular flow efficiency. This study also highlights the sensitivity of 4D flow CMR biomarkers to detect earlier ventricular dysfunction assisting in identification of patients who may benefit from PAS interventions.

Comprehensive non-invasive analysis of lower urinary tract anatomy using MRI.

PURPOSE: Anatomic changes that coincide with aging including benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS) negatively impact quality of life. Use of MRI with its exquisite soft tissue contrast, full field-of-view capabilities, and lack of radiation is uniquely suited for quantifying specific lower urinary tract features and providing comprehensive measurements such as total bladder wall volume (BWV), bladder wall thickness (BWT), and prostate volume (PV). We present a technique for generating 3D anatomical renderings from MRI to perform quantitative analysis of lower urinary tract anatomy. METHODS: T2-weighted fast-spin echo MRI of the pelvis in 117 subjects (59F;58 M) aged 30-69 (49.5 ± 11.3) without known lower urinary tract symptoms was retrospectively segmented using Materialise software. Virtual 3D models were used to measure BWV, BWT, and PV. RESULTS: BWV increased significantly between the 30-39 and 60-69 year age group in women (p = 0.01), but not men (p = 0.32). BWV was higher in men than women aged 30-39 and 40-49 (p = 0.02, 0.05, respectively) ,but not 50-59 or 60-69 (p = 0.18, 0.16, respectively). BWT was thicker in men than women across all age groups. Regional differences in BWT were observed both between men and women and between opposing bladder wall halves (anterior/posterior, dome/base, left/right) within each sex in the 50-59 and 60-69 year groups. PV increased from the 30-39 to 60-69 year groups (p = 0.05). BWT was higher in subjects with enlarged prostates (> 40cm3) (p = 0.05). CONCLUSION: Virtual 3D MRI models of the lower urinary tract reliably quantify sex-specific and age-associated changes of the bladder wall and prostate.

Pulmonary artery and lung parenchymal growth following early versus delayed stent interventions in a swine pulmonary artery stenosis model.

OBJECTIVES: Compare lung parenchymal and pulmonary artery (PA) growth and hemodynamics following early and delayed PA stent interventions for treatment of unilateral branch PA stenosis (PAS) in swine. BACKGROUND: How the pulmonary circulation remodels in response to different durations of hypoperfusion and how much growth and function can be recovered with catheter directed interventions at differing time periods of lung development is not understood. METHODS: A total of 18 swine were assigned to four groups: Sham (n = 4), untreated left PAS (LPAS) (n = 4), early intervention (EI) (n = 5), and delayed intervention (DI) (n = 5). EI had left pulmonary artery (LPA) stenting at 5 weeks (6 kg) with redilation at 10 weeks. DI had stenting at 10 weeks. All underwent right heart catheterization, computed tomography, magnetic resonance imaging, and histology at 20 weeks (55 kg). RESULTS: EI decreased the extent of histologic changes in the left lung as DI had marked alveolar septal and bronchovascular abnormalities (p = .05 and p < .05 vs. sham) that were less prevalent in EI. EI also increased left lung volumes and alveolar counts compared to DI. EI and DI equally restored LPA pulsatility, R heart pressures, and distal LPA growth. EI and DI improved, but did not normalize LPA stenosis diameter (LPA/DAo ratio: Sham 1.27 ± 0.11 mm/mm, DI 0.88 ± 0.10 mm/mm, EI 1.01 ± 0.09 mm/mm) and pulmonary blood flow distributions (LPA-flow%: Sham 52 ± 5%, LPAS 7 ± 2%, DI 44 ± 3%, EI 40 ± 2%). CONCLUSION: In this surgically created PAS model, EI was associated with improved lung parenchymal development compared to DI. Longer durations of L lung hypoperfusion did not detrimentally affect PA growth and R heart hemodynamics. Functional and anatomical discrepancies persist despite successful stent interventions that warrant additional investigation.

Active-Site Druggability of Carbapenemases and Broad-Spectrum Inhibitor Discovery.

Serine and metallo-carbapenemases are a serious health concern due to their capability to hydrolyze nearly all ß-lactam antibiotics. However, the molecular basis for their unique broad-spectrum substrate profile is poorly understood, particularly for serine carbapenemases, such as KPC-2. Using substrates and newly identified small molecules, we compared the ligand binding properties of KPC-2 with the noncarbapenemase CTX-M-14, both of which are Class A ß-lactamases with highly similar active sites. Notably, compared to CTX-M-14, KPC-2 was more potently inhibited by hydrolyzed ß-lactam products (product inhibition), as well as by a series of novel tetrazole-based inhibitors selected from molecular docking against CTX-M-14. Together with complex crystal structures, these data suggest that the KPC-2 active site has an enhanced ability to form favorable interactions with substrates and small molecule ligands due to its increased hydrophobicity and flexibility. Such properties are even more pronounced in metallo-carbapenemases, such as NDM-1, which was also inhibited by some of the novel tetrazole compounds, including one displaying comparable low µM affinities against both KPC-2 and NDM-1. Our results suggest that carbapenemase activity confers an evolutionary advantage on producers via a broad ß-lactam substrate scope but also a mechanistic Achilles' heel that can be exploited for new inhibitor discovery. The complex structures demonstrate, for the first time, how noncovalent inhibitors can be engineered to simultaneously target both serine and metallo-carbapenemases. Despite the relatively modest activity of the current compounds, these studies also demonstrate that hydrolyzed products and tetrazole-based chemotypes can provide valuable starting points for broad-spectrum inhibitor discovery against carbapenemases.

Effect of Dynamic Workstation Use on Radiologist Detection of Pulmonary Nodules on CT.

PURPOSE: The aim of this study was to determine the effects of using a treadmill workstation during CT interpretation on radiologists' sensitivity for lung nodule detection, accuracy and adherence to accepted management recommendations, and examination interpretation time. METHODS: This HIPAA-compliant study was approved by the institutional review board. Three radiologists performed a retrospective review of 55 CT examinations of the chest originally performed for lung cancer screening. These studies were reviewed both while sitting at a conventional workstation and while walking at a treadmill workstation. A separate thoracic radiologist reviewed the examinations at a conventional workstation only to serve as a control. The number of pulmonary nodules detected, accuracy of or adherence to follow-up recommendations, and time required for examination interpretation were recorded and compared between each condition. RESULTS: There was no statistically significant difference in the total number of nodules detected while walking versus seated. Intraobserver follow-up recommendations were consistent to highly consistent between sitting and walking. There was moderate interobserver agreement between the radiologists' recommendation for seated versus walking conditions. There was a statistically significant difference in time taken to complete each examination, with interpretation during walking taking less time than during sitting. CONCLUSIONS: Use of a treadmill workstation does not significantly affect the detection of lung nodules on CT or lead to changes in management recommendations but does decrease examination interpretation time.

Diversity in CO2-Concentrating Mechanisms among Chemolithoautotrophs from the Genera Hydrogenovibrio, Thiomicrorhabdus, and Thiomicrospira, Ubiquitous in Sulfidic Habitats Worldwide.

Members of the genera Hydrogenovibrio, Thiomicrospira, and Thiomicrorhabdus fix carbon at hydrothermal vents, coastal sediments, hypersaline lakes, and other sulfidic habitats. The genome sequences of these ubiquitous and prolific chemolithoautotrophs suggest a surprising diversity of mechanisms for the uptake and fixation of dissolved inorganic carbon (DIC); these mechanisms are verified here. Carboxysomes are apparent in the transmission electron micrographs of most of these organisms but are lacking in Thiomicrorhabdus sp. strain Milos-T2 and Thiomicrorhabdus arctica, and the inability of Thiomicrorhabdus sp. strain Milos-T2 to grow under low-DIC conditions is consistent with the absence of carboxysome loci in its genome. For the remaining organisms, genes encoding potential DIC transporters from four evolutionarily distinct families (Tcr_0853 and Tcr_0854, Chr, SbtA, and SulP) are located downstream of carboxysome loci. Transporter genes collocated with carboxysome loci, as well as some homologs located elsewhere on the chromosomes, had elevated transcript levels under low-DIC conditions, as assayed by reverse transcription-quantitative PCR (qRT-PCR). DIC uptake was measureable via silicone oil centrifugation when a representative of each of the four types of transporter was expressed in Escherichia coli The expression of these genes in the carbonic anhydrase-deficient E. coli strain EDCM636 enabled it to grow under low-DIC conditions, a result consistent with DIC transport by these proteins. The results from this study expand the range of DIC transporters within the SbtA and SulP transporter families, verify DIC uptake by transporters encoded by Tcr_0853 and Tcr_0854 and their homologs, and introduce DIC as a potential substrate for transporters from the Chr family.IMPORTANCE Autotrophic organisms take up and fix DIC, introducing carbon into the biological portion of the global carbon cycle. The mechanisms for DIC uptake and fixation by autotrophic Bacteria and Archaea are likely to be diverse but have been well characterized only for "Cyanobacteria" Based on genome sequences, members of the genera Hydrogenovibrio, Thiomicrospira, and Thiomicrorhabdus have a variety of mechanisms for DIC uptake and fixation. We verified that most of these organisms are capable of growing under low-DIC conditions, when they upregulate carboxysome loci and transporter genes collocated with these loci on their chromosomes. When these genes, which fall into four evolutionarily independent families of transporters, are expressed in E. coli, DIC transport is detected. This expansion in known DIC transporters across four families, from organisms from a variety of environments, provides insight into the ecophysiology of autotrophs, as well as a toolkit for engineering microorganisms for carbon-neutral biochemistries of industrial importance.

A global database of nitrogen and phosphorus excretion rates of aquatic animals.

Animals can be important in modulating ecosystem-level nutrient cycling, although their importance varies greatly among species and ecosystems. Nutrient cycling rates of individual animals represent valuable data for testing the predictions of important frameworks such as the Metabolic Theory of Ecology (MTE) and ecological stoichiometry (ES). They also represent an important set of functional traits that may reflect both environmental and phylogenetic influences. Over the past two decades, studies of animal-mediated nutrient cycling have increased dramatically, especially in aquatic ecosystems. Here we present a global compilation of aquatic animal nutrient excretion rates. The dataset includes 10,534 observations from freshwater and marine animals of N and/or P excretion rates. These observations represent 491 species, including most aquatic phyla. Coverage varies greatly among phyla and other taxonomic levels. The dataset includes information on animal body size, ambient temperature, taxonomic affiliations, and animal body N:P. This data set was used to test predictions of MTE and ES, as described in Vanni and McIntyre (2016; Ecology DOI: 10.1002/ecy.1582).

Structured inquiry-based learning: Drosophila GAL4 enhancer trap characterization in an undergraduate laboratory course.

We have developed and tested two linked but separable structured inquiry exercises using a set of Drosophila melanogaster GAL4 enhancer trap strains for an upper-level undergraduate laboratory methods course at Bucknell University. In the first, students learn to perform inverse PCR to identify the genomic location of the GAL4 insertion, using FlyBase to identify flanking sequences and the primary literature to synthesize current knowledge regarding the nearest gene. In the second, we cross each GAL4 strain to a UAS-CD8-GFP reporter strain, and students perform whole mount CNS dissection, immunohistochemistry, confocal imaging, and analysis of developmental expression patterns. We have found these exercises to be very effective in teaching the uses and limitations of PCR and antibody-based techniques as well as critical reading of the primary literature and scientific writing. Students appreciate the opportunity to apply what they learn by generating novel data of use to the wider research community.

Conscious sedation attitudes and perceptions: a survey of american academy of pediatric dentistry members.

PURPOSE: The purpose of this study was to assess the attitudes and perceptions of the American Academy of Pediatric Dentistry (AAPDM) members regarding conscious sedation. METHODS: A 22-item survey was e-mailed to 4,358 active AAPD members to identify factors that influence pediatric dentists' practice of conscious sedation in their dental offices. Bivariate and logistic regression models were used to analyze data. RESULTS: A total of 1,219 surveys were returned (28% response rate); 743 (63%) respondents practiced conscious sedation. Help in providing dental care for patients difficult to manage was the primary reason reported for practicing conscious sedation. Conversely, not wanting the liability related to conscious sedation was the main reason reported by those who don't sedate. Bivariate and multivariate logistic regression analyses indicated that dentists were significantly more likely to perform conscious sedation if they practiced more than 3 days a week (P>.03), had 11% or more patients with public insurance (P>.02), and rated their sedation training as "good or excellent" (P<.001). CONCLUSIONS: Among respondents, the attitudes of those who practice conscious sedation varied significantly from those who don't with location of the practice and the quality of their sedation training as significant influences on this decision.