Search

Background and Objectives : Patients with pre-existing cardiac disease have a higher prevalence of Obstructive Sleep Apnea (OSA). OSA has been associated with an increased risk of supraventricular and ventricular arrhythmia. We screened subjects with implanted pacemakers and automated implantable cardioverter defibrillators (AICD) for OSA with the Berlin Questionnaire and compared the incidence of ventricular arrhythmias and automated implantable cardioverter defibrillator (AICD) firing between high and low OSA risk groups. Materials and Methods : We contacted 648 consecutive patients from our arrhythmia clinic to participate in the study and performed final analyses on 171 subjects who consented and had follow-up data. Data were abstracted from the electronic health record for the incidence of non-sustained ventricular tachycardia (NSVT), ventricular tachycardia (VT), ventricular fibrillation (VF) and AICD firing and then compared between those at high versus low risk of OSA using the Berlin Questionnaire and multivariate negative binomial regression. Results : The average follow-up period was 24.2 ± 4.4 months. After adjusting for age, gender and history of heart failure, those subjects at high risk of OSA had a higher burden of NSVT vs. those with a low risk of OSA (33.4 ± 96.2 vs. 5.82 ± 17.1 episodes, p = 0.003). A predetermined subgroup analysis of AICD recipients also demonstrated a significantly higher burden of NSVT in the high vs. low OSA risk groups (66.2 ± 128.6 vs. 18.9 ± 36.7 episodes, p = 0.033). There were significant differences in the rates of VT, VF or AICD shock burden between the high and low OSA risk groups and in the AICD subgroup analysis. Conclusions : There was increased ventricular ectopy among pacemaker and AICD recipients at high risk of OSA, but the prevalence of VT, VF or AICD shocks was similar to those with low risk of OSA.

Global Strategy for the Diagnosis, Management, and Prevention of COPD 2018 is a consensus report published periodically since 2001 by an international panel of health professionals from respiratory medicine, socioeconomics, public health, and education comprising the Global Initiative for Chronic Obstructive Lung Disease (GOLD). The GOLD documents endeavor to incorporate latest evidence and expert consensus and are intended for use as "strategy documents" for implementation of effective care for chronic obstructive lung disease (COPD) on a global level. The GOLD 2018 report defines COPD as a "common, preventable and treatable disease that is characterized by persistent respiratory symptoms and airflow limitation that is due to airway and/or alveolar abnormalities, usually caused by significant exposure to noxious particles or gases," with the criteria of "persistent respiratory symptoms" being a new and controversial inclusion since 2017. With the availability of newer pharmacotherapy options, treatment recommendations are made on the basis of a review of the latest literature and directed by symptom burden and health care utilization. Apart from the change in definition, a major shift in the recommendations is the exclusion of severity of airflow limitation as one of the major factors in guiding therapy. We review the salient features of the GOLD 2018 document and provide commentary on features that merit further discussion based on our clinical experience and practice as well as literature review current as of February 2018., (Copyright © 2018 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Lung adenocarcinoma (ADC), the most common lung cancer type, is recognized increasingly as a disease spectrum. To guide individualized patient care, a non-invasive means of distinguishing indolent from aggressive ADC subtypes is needed urgently. Computer-Aided Nodule Assessment and Risk Yield (CANARY) is a novel computed tomography (CT) tool that characterizes early ADCs by detecting nine distinct CT voxel classes, representing a spectrum of lepidic to invasive growth, within an ADC. CANARY characterization has been shown to correlate with ADC histology and patient outcomes. This study evaluated the inter-observer variability of CANARY analysis. Three novice observers segmented and analyzed independently 95 biopsy-confirmed lung ADCs from Vanderbilt University Medical Center/Nashville Veterans Administration Tennessee Valley Healthcare system (VUMC/TVHS) and the Mayo Clinic (Mayo). Inter-observer variability was measured using intra-class correlation coefficient (ICC). The average ICC for all CANARY classes was 0.828 (95% CI 0.76, 0.895) for the VUMC/TVHS cohort, and 0.852 (95% CI 0.804, 0.901) for the Mayo cohort. The most invasive voxel classes had the highest ICC values. To determine whether nodule size influenced inter-observer variability, an additional cohort of 49 sub-centimeter nodules from Mayo were also segmented by three observers, with similar ICC results. Our study demonstrates that CANARY ADC classification between novice CANARY users has an acceptably low degree of variability, and supports the further development of CANARY for clinical application., Competing Interests: FM, TP, BJB, and SR report intellectual property and royalties received from Imbio, LLC (Minneapolis, MN), which licenses CANARY. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The remaining authors have nothing to disclose.

Background: Most patients with restriction have a pulmonary function test (PFT) pattern in which total lung capacity (TLC), FVC, and FEV 1 are reduced to a similar degree. This pattern is called "simple restriction" (SR). In contrast, we commonly observe a pattern in which FVC percent predicted ( pp ) is disproportionately reduced relative to TLC pp . This pattern is termed "complex restriction" (CR), and we attempted to characterize its clinical, radiologic, and physiologic features., Methods: This study reviewed PFT results of patients tested between November 2009 and June 2013 who had restriction (TLC less than the lower limit of normal). SR was defined as TLC pp -FVC pp  ≤ 10%, and CR was stratified into four classes based on TLC pp -FVC pp discrepancy: Class 1 CR, TLC pp -FVC pp > 10% and ≤ 15%; Class 2 CR, TLC pp -FVC pp > 15% and ≤20%; Class 3 CR, TLC pp -FVC pp > 20% and ≤ 25%; and Class 4 CR, TLC pp -FVC pp > 25%. The medical records of 150 randomly selected patients with SR and 50 patients from each CR class were reviewed., Results: Of 39,277 PFTs completed, we identified 4,532 patients (11.5%) with restriction: 2,407 (6.1%) with SR, 1,614 (4.1%) with CR, and 511 (1.3%) with a mixed pattern. Patients with CR were younger, were more often women, and had a higher prevalence of neuromuscular disease, BMI > 40 kg/m 2 or < 18.5 kg/m 2 , diaphragmatic dysfunction, bronchiectasis, CT mosaic attenuation, and pulmonary hypertension (P < .0001, < .0001, < .001, .004, .0008, .002, .008, .009, .053, and .01, respectively) and a lower prevalence of interstitial lung disease (P < .0001)., Conclusions: CR is a common PFT pattern with distinct clinical features. The associated clinical entities share impaired lung emptying (eg, neuromuscular disease, occult obstruction, chest wall limitation). Clinicians should be aware of this novel PFT pattern and how it shapes the differential diagnosis., (Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: A growing body of evidence supports the use of bedside ultrasound for core Internal Medicine procedures and increasingly as augmentation of the physical exam. The literature also supports that trainees, both medical students and residents, can acquire these skills. However, there is no consensus on training approach., Aim: To implement and study the effectiveness of a high-yield and expedited curriculum to train internal medicine interns to use bedside ultrasound for physical examination and procedures., Setting: The study was conducted at a metropolitan, academic medical center and included 33 Internal Medicine interns., Program Description: This was a prospective cohort study of a new educational intervention consisting of a single-day intensive bedside ultrasound workshop followed by two optional hour-long workshops later in the year. The investigation was conducted at Oregon Health & Science University in Portland, Oregon. The intensive day consisted of alternating didactic sessions with small group hands-on ultrasound practice sessions and ultrasound simulations. A 30-question assessment was used to assess ultrasound interpretation knowledge prior to, immediately post, and 6 months post intervention., Results: Thirty-three interns served as their own historical controls. Assessment performance significantly increased after the intervention from a mean pre-test score of 18.3 (60.9 % correct) to a mean post-test score 25.5 (85.0 % correct), P value of <0.0001. This performance remained significantly better at 6 months with a mean score of 23.8 (79.3 % correct), P value <0.0001. There was significant knowledge attrition compared to the immediate post-assessment, P value 0.0099., Conclusions: A single-day ultrasound training session followed by two optional noon conference sessions yielded significantly improved ultrasound interpretation skills in internal medicine interns.

Purpose: This study assessed a novel diabetes mellitus (DM) rating scale in relation to its utility in reducing Descemet membrane endothelial keratoplasty (DMEK) tissue preparation failure., Methods: A 5-point DM rating scale was defined, in which 1 demonstrated relatively good health associated with DM and 5 represented comorbidities associated with DM. A chart review from consecutive donors who had at least 1 tissue prepared for DMEK was performed. Using the donor profile, the first tissue processed from each donor was categorized according to the DM severity and if the tissue passed or failed the DMEK preparation. Failure rates per rating group were evaluated using logistic regression and odds of preparation failure., Results: A total of 125 tissues prepared for DMEK were categorized based on the defined DM rating scale. Of these, 9 tissues were rated 1 (11.1% failure), 25 were rated 2 (0% failure), 31 were rated 3 (6.5% failure), 24 were rated 4 (16.7% failure), and 36 were rated 5 (30.6% failure). The odds ratios were significant for tissues rated as 5 and 3 (P < 0.05). No other rating categories were found to influence the odds of failure. A χ test comparing categories of low risk (1-3) and high risk (4-5) was also performed (P = 0.001)., Conclusions: The DM rating scale does seem to stratify the risk of preparation failure associated with the severity of DM and associated comorbidities. Inclusion of some diabetic donors for the preparation of DMEK grafts may be warranted given proper screening of the donor history and application of the rating scale.

In 2010, the BAX System PCR assay for Salmonella was modified to include a hot start functionality designed to keep the reaction enzyme inactive until PCR begins. To validate the assay's Official Methods of Analysis status to include this procedure modification, an evaluation was conducted on four food types that were simultaneously analyzed with the BAX System and either the U.S. Food and Drug Administration's Bacteriological Analytical Manual or the U.S. Department of Agriculture-Food Safety and Inspection Service Microbiology Laboratory Guidebook reference method for detecting Salmonella. Identical performance between the BAX System method and the reference methods was observed. Additionally, lysates were analyzed using both the BAX System Classic and BAX System Q7 instruments with identical results using both platforms for all samples tested. Of the 100 samples analyzed, 34 samples were positive for both the BAX System and reference methods, and 66 samples were negative by both the BAX System and reference methods, demonstrating 100% correlation. No instrument platform variation was observed. Additional inclusivity and exclusivity testing using the modified test kit demonstrated the test kit to be 100% accurate in evaluation of test panels of 352 Salmonella strains and 46 non-Salmonella strains.

Evaluations were conducted to test the performance of the BAX System Real-Time PCR assay, which was certified as Performance Tested Method 031002 for screening E. coli O157:H7 in ground beef, beef trim, spinach, and lettuce. Method comparison studies performed on samples with low-level inoculates showed that the BAX System demonstrates a sensitivity equivalent or superior to the FDA-BAM and the USDA-FSIS culture methods, but with a significantly shorter time to result. Tests to evaluate inclusivity and exclusivity returned no false-negative and no false-positive results on a diverse panel of isolates, and tests for lot-to-lot variability and tablet stability demonstrated consistent performance. Ruggedness studies determined that none of the factors examined affect the performance of the assay. An accelerated shelf life study determined an initial 36 month shelf life for the test kit.

The new BAX System PCR Assay for Genus Listeria 24E was evaluated for detecting Listeria spp. in frankfurters, spinach, cooked shrimp, queso fresco cheese, and on stainless steel surfaces with a single-stage enrichment in BAX System 24 Listeria Enrichment Broth (24 LEB). Method comparison studies performed on samples with low-level inoculates showed that the BAX System demonstrates a sensitivity equivalent or superior to the U.S. Food and Drug Administration's Bacteriological Analytical Manual and the U.S. Department of Agriculture-Food Safety and Inspection Service culture methods, but with a significantly shorter time to result. Tests to evaluate inclusivity and exclusivity returned no false-negative and no false-positive results on a diverse panel of isolates, and tests for lot-to-lot variability and tablet stability demonstrated consistent performance. Ruggedness studies determined that none of the factors examined, within the range of deviations from specified parameters examined, affect the performance of the assay.

The BAX System PCR assay for Salmonella detection in foods was previously validated as AOAC Research Institute (RI) Performance Tested Method (PTM) 100201. New studies were conducted on beef and produce using the same media and protocol currently approved for the BAX System PCR assay for E. coli O157:H7 multiplex (MP). Additionally, soy protein isolate was tested for matrix extension using the U.S. Food and Drug Administration-Bacteriological Analytical Manual (FDA-BAM) enrichment protocols. The studies compared the BAX System method to the U.S. Department of Agriculture culture method for detecting Salmonella in beef and the FDA-BAM culture method for detecting Salmonella in produce and soy protein isolate. Method comparison studies on low-level inoculates showed that the BAX System assay for Salmonella performed as well as or better than the reference method for detecting Salmonella in beef and produce in 8-24 h enrichment when the BAX System E. coli O157:H7 MP media was used, and soy protein isolate in 20 h enrichment with lactose broth followed by 3 h regrowth in brain heart infusion broth. An inclusivity panel of 104 Salmonella strains with diverse serotypes was tested by the BAX System using the proprietary BAX System media and returned all positive results. Ruggedness factors involved in the enrichment phase were also evaluated by testing outside the specified parameters, and none of the factors examined affected the performance of the assay.

Evaluations were conducted to test the performance of the BAX System PCR assay which was certified as Performance Tested Method 010902 for screening yeast and mold in yogurt, corn starch, and milk-based powdered infant formula. Method comparison studies performed on samples with low-level inoculates showed that the BAX System demonstrates a sensitivity equivalent to the U.S. Food and Drug Administration's Bacteriological Analytical Manual culture method, but with a significantly shorter time to obtain results. Tests to evaluate inclusivity and exclusivity returned no false-negative and no false-positive results on a diverse panel of isolates, and tests for lot-to-lot variability and tablet stability demonstrated consistent performance. Ruggedness studies determined that none of the factors examined affected the performance of the assay.

Methylomonas sp. strain 16a is an obligate methanotrophic bacterium that uses methane or methanol as the sole carbon source. An effort was made to engineer this organism for astaxanthin production. Upon expressing the canthaxanthin gene cluster under the control of the native hps promoter in the chromosome, canthaxanthin was produced as the main carotenoid. Further conversion to astaxanthin was carried out by expressing different combinations of crtW and crtZ genes encoding the beta-carotenoid ketolase and hydroxylase. The carotenoid intermediate profile was influenced by the copy number of these two genes under the control of the hps promoter. Expression of two copies of crtZ and one copy of crtW led to the accumulation of a large amount of the mono-ketolated product adonixanthin. On the other hand, expression of two copies of crtW and one copy of crtZ resulted in the presence of non-hydroxylated carotenoid canthaxanthin and the mono-hydroxylated adonirubin. Production of astaxanthin as the predominant carotenoid was obtained in a strain containing two complete sets of carotenoid biosynthetic genes. This strain had an astaxanthin titer ranging from 1 to 2.4 mg g(-1) of dry cell biomass depending on the growth conditions. More than 90% of the total carotenoid was astaxanthin, of which the majority was in the form of E-isomer. This result indicates that it is possible to produce astaxanthin with desirable properties in methanotrophs through genetic engineering.

A sensitive and selective LC-MS-MS method for the determination of DPC 423 (I), an antithrombotic agent, is described. This method used a solid-phase extraction from 0.1 ml plasma with an Isolute C(2) cartridge. HPLC separation was carried out on a YMC ODS-AQ C(18) column (50x2 mm) at a flow-rate of 300 microliter/min with an analysis time of 5 min. Compounds were eluted using a mobile phase of H(2)O/CH(3)CN/HCOOH: 66:34:0.1 (v/v/v), pH 4.0. A structural analogue of I was used as the internal standard to account for variations in recovery and instrument response. Mass spectrometric detection was carried out with a PE Sciex API III(+) triple quadrupole mass spectrometer equipped with a Turbo IonSpray source as the LC-MS interface. Good intra-day and inter-day assay precision (<10% CV) and accuracy (<10% difference) were observed over a concentration range of 0.005-2.5 microM in plasma. The extraction recoveries were approximately 90% and the method was found to be linear for the assay (r(2)>0.999). The method has been successfully applied to discovery and preclinical pharmacokinetic studies, including a dose range-finding study and toxicokinetic exposure studies in rat and dog.

Presenilins (PS) are involved in gamma-secretase-mediated processing of beta-amyloid precursor protein (APP) and the Notch family of proteins. In addition, presenilin 1 (PS-1) binds to members of the armadillo family of proteins. In this study the relationship between PS-1-mediated proteolytic activity and PS-1-mediated regulation of beta-catenin function was investigated. Incubation of cells with a potent, small molecule gamma-secretase inhibitor did not affect PS-1/beta-catenin interaction as determined by co-immunoprecipitation, or affect the regulation of beta-catenin turnover, as determined by pulse-chase analysis, even at inhibitor concentrations that completely blocked PS-mediated APP processing. Moreover, inhibition of PS-1-mediated proteolytic activity did not affect beta-catenin trafficking, as determined by immunolocalization and immunoblotting, or beta-catenin-mediated transcription. These results indicate that PS-1-mediated regulation of gamma-secretase activity and PS-1-mediated regulation of beta-catenin function can be pharmacologically separated and support the idea that these are distinct functions.

The purpose of the present study was to assess the magnitude and stability of a number of functional deficits in rats subjected to occlusion of the middle cerebral artery (MCAO). Three groups of rats, treated with 90-min, 120-min, or sham occlusion were used in functional studies for 22 weeks following surgery. The following tests were used: methamphetamine-induced rotation, the staircase test, acquisition of operant responding, running-wheel behavior, and performance of operant differential reinforcement of a low-rate responding (DRL) schedule of reinforcement. Histology performed at 23 weeks following infarct showed on average modest damage of a 19% reduction in hemispheric volume. Of the behavioral tests conducted, rotation, the staircase test, and the operant DRL were sensitive to ischemic damage, and were under some circumstances related to lesion size. These data show that long-term functional deficits following MCAO are demonstrable, and hence, assessment of long-term neuroprotection is feasible.