Compressed sensing with signal averaging for improved sensitivity and motion artifact reduction in fluorine‐19 MRI

Fluorine‐19 (¹⁹F) MRI of injected perfluorocarbon emulsions (PFCs) allows for the non‐invasive quantification of inflammation and cell tracking, but suffers from a low signal‐to‐noise ratio and extended scan time. To address this limitation, we tested the hypotheses that a ¹⁹F MRI pulse sequence that combines a specific undersampling regime with signal averaging has both increased sensitivity and robustness against motion artifacts compared with a non‐averaged fully sampled pulse sequence, when both datasets are reconstructed with compressed sensing. As a proof of principle, numerical simulations and phantom experiments were performed on selected variable ranges to characterize the point spread function of undersampling patterns, as well as the vulnerability to noise of undersampling and reconstruction parameters with paired numbers of x signal averages and acceleration factor x (NAx ‐AFx ). The numerical simulations demonstrated that a probability density function that uses 25% of the samples to fully sample the k‐space central area allowed for an optimal balance between limited blurring and artifact incoherence. At all investigated noise levels, the Dice similarity coefficient (DSC) strongly depended on the regularization parameters and acceleration factor. In phantoms, the motion robustness of an NA8‐AF8 undersampling pattern versus NA1‐AF1 was evaluated with simulated and real motion patterns. Differences were assessed with the DSC, which was consistently higher for the NA8‐AF8 compared with the NA1‐AF1 strategy, for both simulated and real cyclic motion patterns (P < 0.001). Both strategies were validated in vivo in mice (n = 2) injected with perfluoropolyether. Here, the images displayed a sharper delineation of the liver with the NA8‐AF8 strategy than with the NA1‐AF1 strategy. In conclusion, we validated the hypotheses that in ¹⁹F MRI the combination of undersampling and averaging improves both the sensitivity and the robustness against motion artifacts.     

Functional roles of oral reflexes in chewing and biting: phase-, task- and site-dependent reflex sensitivity

Because loading during chewing is not totally predictable and jaw-closing muscles are strong and act over short distances, feedback from oral receptors is important in the control of mastication. Information on such feedback can be obtained by studying reflexes in jaw muscle EMGs. This review will deal with the contribution of reflex mechanisms to modifying motor neuron activity during chewing, and the dependency of reflex sensitivity on motor task, phase of movement, and site of stimulation.     

Improving Mutation Screening in Familial Hematuric Nephropathies through Next Generation Sequencing

Alport syndrome is an inherited nephropathy associated with mutations in genes encoding type IV collagen chains present in the glomerular basement membrane. COL4A5 mutations are associated with the major X-linked form of the disease, and COL4A3 and COL4A4 mutations are associated with autosomal recessive and dominant forms (thought to be involved in 15% and 1%–5% of the families, respectively) and benign familial hematuria. Mutation screening of these three large genes is time-consuming and expensive. Here, we carried out a combination of multiplex PCR, amplicon quantification, and next generation sequencing (NGS) analysis of three genes in 101 unrelated patients. We identified 88 mutations and 6 variations of unknown significance on 116 alleles in 83 patients. Two additional indel mutations were found only by secondary Sanger sequencing, but they were easily identified retrospectively with the web-based sequence visualization tool Integrative Genomics Viewer. Altogether, 75 mutations were novel. Sequencing the three genes simultaneously was particularly advantageous as the mode of inheritance could not be determined with certainty in many instances. The proportion of mutations in COL4A3 and COL4A4 was notably high, and the autosomal dominant forms of Alport syndrome appear more frequently than reported previously. Finally, this approach allowed the identification of large COL4A3 and COL4A4 rearrangements not described previously. We conclude that NGS is efficient, reduces screening time and cost, and facilitates the provision of appropriate genetic counseling in Alport syndrome.     

Optimal pressure support level for beginning weaning in patients with COPD: Measurement of diaphragmatic activity with step-by-step decreasing pressure support level

The study objective was to determine an “optimal” individual pressure support (PS) level for beginning weaning with PS ventilation in patients with chronic obstructive pulmonary disease (COPD). Eleven COPD patients intubated and ventilated for acute respiratory failure and judged ready for weaning were studied. The technique consisted of lowering the PS level from a point that was characteristic for each patient and measurable under controlled mechanical ventilation, after setting the ventilator as recommended for COPD patients judged ready for weaning, that is, peak inflation pressure (PIP). This determination was based mainly on exploring the diaphragm with an electromyographic technique by defining the optimal PS level as the lowest PS level associated with no EMG evidence of diaphragmatic stress. Diaphragmatic electromyographic activity (diEMG) was recorded by a bipolar esophageal electrode (Disa-Denmark), and the high-frequency electrical component/low-frequency ratio (H/L) was calculated. The reference H/L was determined during a few spontaneous ventilatory cycles. Muscle stress was defined as a greater than 20% reduction in H/L compared with the reference value. Optimal PS levels ranged from 4 to 24 cm H₂O with a mean of 14 ± 6 cm H₂O. Two patients with optimal PS level at 4 cm H₂O did not require weaning and were quickly extubated. For the nine other patients, optimal PS levels were found to be 70% of PIP; in none was it necessary during weaning to use PS levels higher than individual optimal PS levels. Optimal PS level established with di-EMG monitoring seems to be a useful index for beginning weaning in the PS ventilation mode in COPD patients. The hypothesis of beginning weaning with a PS level equal to 70% of PIP needs to be tested.     

Multiple-dose halazepam kinetics

Halazepam is a benzodiazepine used in the management of anxiety disorders or short-term relief of anxiety. Our study was undertaken to evaluate its steady-state kinetics and those of its major active plasma metabolite N- desalkylhalazepam . Eleven healthy men aged 19 to 35 yr were given oral, 40-mg halazepam tablets every 8 hr for 14 days. Plasma samples were analyzed by gas chromatography to determine levels of halazepam and N- desalkylhalazepam . Halazepam kinetics can best be described by a two-compartment open model with first-order absorption kinetics. The elimination phase t1/2s of halazepam and N- desalkylhalazepam were 34.7 and 57.9 hr. Steady-state levels were predictable from kinetic data and were reached by the third day for halazepam and by the eleventh day for N- desalkylhalazepam .     

Cervical and Vaginal Flora Specimens Are Highly Concordant with Respect to Bacterial Vaginosis-Associated Organisms and Commensal Lactobacillus Species in Women of Reproductive Age

Matched vaginal and cervical specimens from 96 subjects were analyzed by quantitative PCR for the presence and concentration of bacterial vaginosis-associated microbes and commensal Lactobacillus spp. Detection of these microbes was 92% concordant, indicating that microbial floras at these body sites are generally similar.     

Development and Validation of a Highly Accurate Quantitative Real-Time PCR Assay for Diagnosis of Bacterial Vaginosis

Bacterial vaginosis (BV) is the most common gynecological infection in the United States. Diagnosis based on Amsel''s criteria can be challenging and can be aided by laboratory-based testing. A standard method for diagnosis in research studies is enumeration of bacterial morphotypes of a Gram-stained vaginal smear (i.e., Nugent scoring). However, this technique is subjective, requires specialized training, and is not widely available. Therefore, a highly accurate molecular assay for the diagnosis of BV would be of great utility. We analyzed 385 vaginal specimens collected prospectively from subjects who were evaluated for BV by clinical signs and Nugent scoring. We analyzed quantitative real-time PCR (qPCR) assays on DNA extracted from these specimens to quantify nine organisms associated with vaginal health or disease: Gardnerella vaginalis, Atopobium vaginae, BV-associated bacteria 2 (BVAB2, an uncultured member of the order Clostridiales), Megasphaera phylotype 1 or 2, Lactobacillus iners, Lactobacillus crispatus, Lactobacillus gasseri, and Lactobacillus jensenii. We generated a logistic regression model that identified G. vaginalis, A. vaginae, and Megasphaera phylotypes 1 and 2 as the organisms for which quantification provided the most accurate diagnosis of symptomatic BV, as defined by Amsel''s criteria and Nugent scoring, with 92% sensitivity, 95% specificity, 94% positive predictive value, and 94% negative predictive value. The inclusion of Lactobacillus spp. did not contribute sufficiently to the quantitative model for symptomatic BV detection. This molecular assay is a highly accurate laboratory tool to assist in the diagnosis of symptomatic BV.     

HIV testing in an ethnically diverse sample of American university students: associations with violence/abuse and covariates

Associations linking HIV infection to violence and abuse are well documented; however, little is known about how violence/abuse is related to HIV testing behavior, particularly among undergraduate university students, who test at lower rates compared to non-student peers in the United States. We assessed history of HIV testing in an ethnically diverse sample of undergraduates in California (n = 1,210); and examined potential associations between testing and various forms of violence/abuse, while controlling for covariates. Whereas 73.4 % of students were sexually active in the past year, only 26.3 % had ever tested for HIV. At the bivariate level, testing was associated with experiencing verbal abuse and sexual violence/coercion, and perpetrating verbal abuse. Experiencing verbal abuse remained significant in multivariate analysis. We discuss findings in a syndemics framework, considered in combination with social psychology-based health behavior theories. Enhanced HIV testing scale-up initiatives for undergraduates are needed and should consider integration with violence prevention programs.