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Amy CS Pearson,1 Rajat N Moman,2 Susan M Moeschler,3 Jason S Eldrige,3 W Michael Hooten3 1Department of Anesthesiology & Perioperative Medicine, Mayo School of Graduate Medical Education, Mayo Clinic, 2Mayo Clinic School of Medicine, 3Department of Anesthesiology & Perioperative Medicine, Mayo College of Medicine, Rochester, MN, USA Introduction: Many providers report lack of confidence in managing patients with chronic pain. Thus, the primary aim of this study was to investigate the associations of provider confidence in managing chronic pain with their practice behaviors and demographics.Materials and methods: The primary outcome measure was the results of the Opioid Therapy Provider Survey, which was administered to clinicians attending a pain-focused continuing medical education conference. Nonparametric correlations were assessed using Spearman’s rho.Results: Of the respondents, 55.0% were women, 92.8% were white, and 56.5% were physicians. Primary care providers accounted for 56.5% of the total respondents. The majority of respondents (60.8%) did not feel confident managing patients with chronic pain. Provider confidence in managing chronic pain was positively correlated with 1) following an opioid therapy protocol (P=0.001), 2) the perceived ability to identify patients at risk for opioid misuse (P=0.006), and 3) using a consistent practice-based approach to improve their comfort level with prescribing opioids (P

W Michael Hooten,1 Jodie Dvorkin,2 Nafisseh S Warner,1 Amy CS Pearson,3 M Hassan Murad,4 David O Warner11Department of Anesthesiology and Perioperative Medicine, Mayo Clinic College of Medicine, Rochester, MN, USA; 2Institute for Clinical Systems Improvement, Minneapolis, MN, USA; 3Department of Anesthesia, University of Iowa Carver College of Medicine, Iowa City, IA, USA; 4Department of Medicine, Mayo Clinic College of Medicine, Rochester, MN, USABackground: The primary objective of this systematic review was to identify the characteristics of physicians who prescribe opioids to adults with chronic pain. This review was limited to studies examining fully-trained physicians, as relevant characteristics of resident physicians and non-physician clinicians may differ.Methods: A comprehensive search of databases from January 1, 1980 to December 5, 2017 was conducted. Eligible study designs included (1) randomized trials; (2) nonrandomized prospective and retrospective studies; and (3) cross-sectional observational studies. The risk of bias in the included studies was assessed using an adapted version of the Newcastle-Ottawa Scale for cross-sectional studies. A total of 2508 records were screened and 22 studies met inclusion criteria. The majority of studies were cross-sectional (n=20) and the total number of participants was 8433.Results: The risk of bias was high overall. The majority of physicians were confident managing and prescribing opioids for chronic pain but had high levels of dissatisfaction. Physicians reported high awareness of the potential for opioid misuse and were concerned about inadequate prior training in pain management. The majority of physicians were less likely to prescribe for patients with a history of substance abuse and reported major concerns about regulatory scrutiny.Conclusion: This systematic review provides the foundation for the development of prospective studies aimed at further elucidating the constellation of mechanisms that influence physicians who manage pain and prescribe opioids.Keywords: systematic review, opioid, prescription, physician characteristics

Amy CS Pearson, Jason S Eldrige, Susan M Moeschler, W Michael Hooten Department of Anesthesiology, Mayo Clinic, Rochester, MN, USA Introduction: Although the majority of opioids in the US are prescribed by nonpain specialists, these providers often report inadequate training in chronic pain management and opioid prescribing. The extent of health care providers' knowledge of opioid prescribing for chronic pain has not been well established. The purpose of this study was to assess knowledge about the use of opioids for chronic pain among health care providers seeking pain-focused continuing medical education. Materials and methods: The study participants (n=131) were recruited at a pain-focused continuing medical education conference for nonpain specialists. Upon commencement of the conference, the KnowPain-50 survey was completed. The survey comprised 50 questions, and 18 questions were related to opioid management. The focus of each opioid question was further categorized as either medicolegal (n=7) or clinical (n=11). Results: The majority of study participants were male physicians with a mean age of 51.8 years. The proportion of correct responses to the 50-item survey was 72%. The proportion of correct responses to the 32 nonopioid questions was 74%, and the proportion of correct responses to the 18 opioid questions was 69% (P

Cardiolipin (CL) is an essential phospholipid that supports the functions of mitochondrial membrane transporters and oxidative phosphorylation complexes. Due to the high level of fatty acyl chain unsaturation, CL is prone to peroxidation during aging, neurodegenerative disease, stroke, and traumatic brain or spinal cord injury. Therefore, effective therapies that stabilize and preserve CL levels or enhance healthy CL fatty acyl chain remodeling are needed. In the last few years, great strides have been made in determining the mechanisms through which precursors for CL biosynthesis, such as phosphatidic acid (PA), are transferred from the ER to the outer mitochondrial membrane (OMM) and then to the inner mitochondrial membrane (IMM) where CL biosynthesis takes place. Many neurodegenerative disorders show dysfunctional mitochondrial ER contact sites that may perturb PA transport and CL biosynthesis. However, little is currently known on how neuronal mitochondria regulate the synthesis, remodeling, and degradation of CL. This review will focus on recent developments on the role of CL in neurological disorders. Importantly, due to CL species in the brain being more unsaturated and diverse than in other tissues, this review will also identify areas where more research is needed to determine a complete picture of brain and spinal cord CL function so that effective therapeutics can be developed to restore the rates of CL synthesis and remodeling in neurological disorders., Competing Interests: Declarations Ethics Approval Not applicable. Consent to Participate Not applicable. Consent for Publication Not applicable. Competing Interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

A long-lived species of zooplankton microcrustaceans, Daphnia magna, sometimes exhibits late-life rebound of reproduction, briefly reversing reproductive senescence. Such events are often interpreted as terminal investments in anticipation of imminent mortality. We demonstrate that such post-senescence reproductive events (PSREs) neither cause nor anticipate increased mortality. We analyze an RNAseq experiment comparing young, old reproductively senescent, and old PSRE Daphnia females. We first show that overall age-related transcriptional changes are dominated by the increased transcription of guanidine monophosphate synthases and guanylate cyclases, as well as two groups of presumed transposon-encoded proteins, and by a drop in transcription of protein synthesis-related genes. We then focus on gene families and functional groups in which full or partial reversal of age-related transcriptional changes occur. This analysis reveals a reversal, in the PSRE individuals, of age-related up-regulation of apolipoproteins D, lysosomal lipases, and peptidases as well as several proteins related to mitochondrial and muscle functions. While it is not certain which of these changes enable reproductive rejuvenation, and which are by-products of processes that lead to it, we present some evidence that post-senescence reproductive events are associated with the reversal of age-related protein and lipid aggregates removal and apoptosis., (© 2024. The Author(s), under exclusive licence to American Aging Association.)

Stress-related and substance use disorders are both characterized by disruptions in reward-related behaviors, and these disorders are often comorbid with one another. Recent investigations have identified a novel mechanism of inhibitory plasticity induced by both stress and substance use within the ventral tegmental area (VTA), a key region in reward processing. This mechanism involves the neuron-specific potassium chloride cotransporter isoform 2 (KCC2), which is essential in modulating inhibitory signaling through the regulation of intracellular chloride (Cl - ) in VTA GABA neurons. Experiences, such as exposure to stress or substance use, diminish KCC2 expression in VTA GABA neurons, leading to abnormal reward-related behaviors. Here, we review literature suggesting that KCC2 downregulation contributes to irregular dopamine (DA) transmission, impacting multiple reward circuits and promoting maladaptive behaviors. Activating KCC2 restores canonical GABA functioning and reduces behavioral deficits in preclinical models, leading us to advocate for KCC2 as a target for therapies aimed at alleviating and mitigating various stress-related and substance use disorders., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Studies of longevity rely on baseline life expectancy of reference genotypes measured in standardized conditions. Variation among labs, protocols, and genotypes makes longevity intervention studies difficult to compare. Furthermore, extending lifespan under suboptimal conditions or that of a short-lived genotype may be of a lesser theoretical and translational value than extending the maximal possible lifespan. Daphnia is becoming a model organism of choice for longevity research complementing data obtained on traditional models. In this study, we report longevity of several genotypes of a long-lived species D. magna under a variety of protocols, aiming to document the highest lifespan, factors reducing it, and parameters that change with age and correlate with longevity. Combining longevity data from 25 experiments across two labs, we report a strong intraspecific variation, moderate effects of group size and medium composition, and strong genotype-by-environment interactions with respect to food level. Specifically, short-lived genotypes show no caloric restriction (CR) effect, while long-lived ones expand their lifespan even further under CR. We find that the CR non-responsive clones show little correlation between longevity and two measures of lipid peroxidation. In contrast, the long-lived, CR-responsive clones show a positive correlation between longevity and lipid hydroperoxide abundance, and a negative correlation with MDA concentration. This indicates differences among genotypes in age-related accumulation and detoxification of LPO products and their effects on longevity. Our observations support the hypothesis that a long lifespan can be affected by CR and levels of oxidative damage, while genetically determined short lifespan remains short regardless., (© 2024. The Author(s), under exclusive licence to American Aging Association.)

Neurotensin (NTS) is a 13-amino acid peptide which is highly expressed in the mammalian ovary in response to the luteinizing hormone surge. Antibody neutralization of NTS in the ovulatory follicle of the cynomolgus macaque impairs ovulation and induces follicular vascular dysregulation, with excessive pooling of red blood cells in the follicle antrum. We hypothesize that NTS is an essential intrafollicular regulator of vascular permeability. In the present study, follicle injection of the NTS receptor antagonist SR142948 also resulted in vascular dysregulation. To measure vascular permeability changes in vitro, primary macaque ovarian microvascular endothelial cells (mOMECs) were enriched from follicle aspirates and studied in vitro. When treated with NTS, permeability of mOMECs decreased. RNA sequencing (RNA-Seq) of mOMECs revealed high mRNA expression of the permeability-regulating adherens junction proteins N-cadherin (CDH2) and K-cadherin (CDH6). Immunofluorescent detection of CDH2 and CDH6 confirmed expression and localized these cadherins to the cell-cell boundaries, consistent with function as components of adherens junctions. mOMECs did not express detectable levels of the typical vascular endothelial cadherin, VE-cadherin (CDH5) as determined by RNA-Seq, qPCR, western blot, and immunofluorescence. Knockdown of CDH2 or CDH6 via siRNA abrogated the NTS effect on mOMEC permeability. Collectively, these data suggest that NTS plays an ovulation-critical role in vascular permeability maintenance, and that CDH2 and CDH6 are involved in the permeability modulating effect of NTS on the ovarian microvasculature. NTS can be added to a growing number of angiogenic regulators which are critical for successful ovulation., (© 2024 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

Purpose: Cochlear implant (CI) recipients with hearing preservation experience significant improvements in speech recognition with electric-acoustic stimulation (EAS) as compared to with a CI alone, although outcomes across EAS users vary. The individual differences in performance may be due in part to default mapping procedures, which result in electric frequency-to-place mismatches for the majority of EAS users. This study assessed the influence of electric mismatches on the early speech recognition for EAS users., Method: Twenty-one participants were randomized at EAS activation to listen exclusively with a default or place-based map. For both groups, the unaided thresholds determined the acoustic cutoff frequency (i.e., > 65 dB HL). For default maps, the electric filter frequencies were assigned to avoid spectral gaps in frequency information but created varying magnitudes of mismatches. For place-based maps, the electric filter frequencies were assigned to avoid frequency-to-place mismatches. Recognition of consonant-nucleus-consonant words and vowels was assessed at activation and 1, 3, and 6 months postactivation., Results: For participants with default maps, electric mismatch at 1500 Hz ranged from 2 to -12.0 semitones ( Mdn = -5 semitones). Poorer performance was observed for those with larger magnitudes of electric mismatch. This effect was observed through 6 months of EAS listening experience., Conclusions: The present sample of EAS users experienced better initial performance when electric mismatches were small or eliminated. These data suggest the utility of methods that reduce electric mismatches, such as place-based mapping procedures. Investigation is ongoing to determine whether these differences persist with long-term EAS use., Supplemental Material: https://doi.org/10.23641/asha.22096523.

Angiogenesis within the ovarian follicle is an important component of ovulation. New capillary growth is initiated by the ovulatory surge of luteinizing hormone (LH), and angiogenesis is well underway at the time of follicle rupture. LH-stimulated follicular production of vascular growth factors has been shown to promote new capillary formation in the ovulatory follicle. The possibility that LH acts directly on ovarian endothelial cells to promote ovulatory angiogenesis has not been addressed. For these studies, ovaries containing ovulatory follicles were obtained from cynomolgus macaques and used for histological examination of ovarian vascular endothelial cells, and monkey ovarian microvascular endothelial cells (mOMECs) were enriched from ovulatory follicles for in vitro studies. mOMECs expressed LHCGR mRNA and protein, and immunostaining confirmed LHCGR protein in endothelial cells of ovulatory follicles in vivo. Human chorionic gonadotropin (hCG), a ligand for LHCGR, increased mOMEC proliferation, migration and capillary-like sprout formation in vitro. Treatment of mOMECs with hCG increased cAMP, a common intracellular signal generated by LHCGR activation. The cAMP analog dibutyryl cAMP increased mOMEC proliferation in the absence of hCG. Both the protein kinase A (PKA) inhibitor H89 and the phospholipase C (PLC) inhibitor U73122 blocked hCG-stimulated mOMEC proliferation, suggesting that multiple G-proteins may mediate LHCGR action. Human ovarian microvascular endothelial cells (hOMECs) enriched from ovarian aspirates obtained from healthy oocyte donors also expressed LHCGR. hOMECs also migrated and proliferated in response to hCG. Overall, these findings indicate that the LH surge may directly activate ovarian endothelial cells to stimulate angiogenesis of the ovulatory follicle., (© The Author(s) 2022. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Bacterial pneumonia is a major risk factor for acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Pseudomonas aeruginosa (PA), an opportunistic pathogen with an increasing resistance acquired against multiple drugs, is one of the main causative agents of ALI and ARDS in diverse clinical settings. Given the anti-inflammatory role of the cannabinoid-2 receptor (CB2R), the effect of CB2R activation in the regulation of PA-induced ALI and inflammation was tested in a mouse model as an alternative to conventional antibiotic therapy., Methods: In order to activate CB2R, a selective synthetic agonist, JWH133, was administered intraperitoneally (i.p.) to C57BL/6J mice. Furthermore, SR144528 (a selective CB2R antagonist) was administered in combination with JWH133 to test the specificity of the CB2R-mediated effect. PA was administered intratracheally (i.t.) for induction of pneumonia in mice. At 24 h after PA exposure, lung mechanics were measured using the FlexiVent system. The total cell number, protein content, and neutrophil population in the bronchoalveolar lavage fluid (BALF) were determined. The bacterial load in the whole lung was also measured. Lung injury was evaluated by histological examination and PA-induced inflammation was assessed by measuring the levels of BALF cytokines and chemokines. Neutrophil activation (examined by immunofluorescence and immunoblot) and PA-induced inflammatory signaling (analyzed by immunoblot) were also studied., Results: CB2R activation by JWH133 was found to significantly reduce PA-induced ALI and the bacterial burden. CB2R activation also suppressed the PA-induced increase in immune cell infiltration, neutrophil population, and inflammatory cytokines. These effects were abrogated by a CB2R antagonist, SR144528, further confirming the specificity of the CB2R-mediated effects. CB2R-knock out (CB2RKO) mice had a significantly higher level of PA-induced inflammation as compared to that in WT mice. CB2R activation diminished the excess activation of neutrophils, whereas mice lacking CB2R had elevated neutrophil activation. Pharmacological activation of CB2R significantly reduced the PA-induced NF-κB and NLRP3 inflammasome activation, whereas CB2KO mice had elevated NLRP3 inflammasome., Conclusion: Our findings indicate that CB2R activation ameliorates PA-induced lung injury and inflammation, thus paving the path for new therapeutic avenues against PA pneumonia., (© 2022. The Author(s).)

The homeless population in the United States is rapidly aging, with a parallel increase in Alzheimer's disease and related dementia (ADRD). During an evolving pandemic that jeopardizes employment and housing, assessing the relationship between ADRD and homelessness is critical since the latter is potentially intervenable. The objective of this study is to review the literature and determine whether there is an association between homelessness and dementia risk. A systematic review of existing studies was conducted through PubMED, SCOPUS, and EMBASE among others. Of the 228 results found, nine met inclusion criteria. Homeless studies mainly centered on veteran populations ( n = 6/9). There is a complex relationship suggesting homelessness as a risk for and consequence of ADRD but also co-occurrence with psychiatric disorders, substance abuse, and traumatic injuries. Future studies should employ enumeration surveys with modular longitudinal tracking and measure social determinants of health, discrimination, chronic stress, and mood disorders.

Background Female surgeons reportedly receive less surgical block time and fewer procedural referrals than male surgeons. In this study, we compared operative days between female and male surgeons throughout Florida. Our objective was to facilitate benchmarking by multispecialty groups, both the endpoint to use for statistically reliable results and expected differences. Methodology The historical cohort study included all 4,060,070 ambulatory procedural encounters and inpatient elective surgical states performed between January 2017 and December 2019 by 8,472 surgeons at 609 facilities. Surgeons' gender, year of medical school graduation, and surgical specialty were obtained from their National Provider Identifiers. Results Female surgeons operated an average of 1.0 fewer days per month than matched male surgeons (99% confidence interval 0.8 to 1.2 fewer days, P < 0.0001). The mean differences were 0.8 to 1.4 fewer days per month among each of the five quintiles of years of graduation from medical school (all P ≤ 0.0050). Results were comparable when repeated using the number of monthly cases the surgeons performed. Conclusions An average difference of ≤1.4 days per month is a conservative estimate for the current status quo of the workload difference in Florida. Suppose that a group's female surgeons average more than two fewer operative days per month than the group's male surgeons of the same specialty. Such a large average difference would call for investigation of what might reflect systematic bias. While such a difference may reflect good flexibility of the organization, it may show a lack of responsiveness (e.g., fewer referrals of procedural patients to female surgeons or bias when apportioning allocated operating room time)., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Dexter et al.)

Geographic variation in thermal tolerance in Daphnia seems to represent genetic load at the loci specifically responsible for heat tolerance resulting from conditional neutrality. We see no evidence of trade-offs between fitness-related traits at 25 °C vs. 10 °C or between two algal diets across Daphnia magna clones from a variety of locations representing the opposite ends of the distribution of long-term heat tolerance. Likewise, we found no evidence of within-environment trade-offs between heat tolerance and fitness-related traits in any of the environments. Neither short-term and long-term heat tolerance shows any consistent relationship with lipid fluorescence polarization and lipid peroxidation across clones or environments. Pervasive positive correlations between fitness-related traits indicate differences in genetic load rather than trade-off based local adaptation or thermal specialization. For heat tolerance such differences may be caused by either relaxation of stabilizing selection due to lower exposure to high temperature extremes, i.e., conditional neutrality, or by small effective population size followed by the recent range expansion., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Respiration rates of ectothermic organisms are affected by environmental temperatures, and sustainable metabolism at high temperatures sometimes limits heat tolerance. Organisms are hypothesized to exhibit acclimatory metabolic compensation effects, decelerating their metabolic processes below Arrhenius expectations based on temperature alone. We tested the hypothesis that either heritable or plastic heat tolerance differences can be explained by metabolic compensation in the eurythermal freshwater zooplankton crustacean Daphnia magna We measured respiration rates in a ramp-up experiment over a range of assay temperatures (5-37°C) in eight genotypes of D . magna representing a range of previously reported acute heat tolerances and, at a narrower range of temperatures (10-35°C), in D . magna with different acclimation history (either 10 or 25°C). We discovered no difference in temperature-specific respiration rates between heat-tolerant and heat-sensitive genotypes. In contrast, we observed acclimation-specific compensatory differences in respiration rates at both extremes of the temperature range studied. Notably, there was a deceleration of oxygen consumption at higher temperature in 25°C-acclimated D . magna relative to their 10°C-acclimated counterparts, observed in active animals, a pattern corroborated by similar changes in filtering rate and, partly, by changes in mitochondrial membrane potential. A recovery experiment indicated that the reduction of respiration was not caused by irreversible damage during exposure to a sublethal temperature. Response time necessary to acquire the respiratory adjustment to high temperature was lower than for low temperature, indicating that metabolic compensation at lower temperatures requires slower, possibly structural changes., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2021. Published by The Company of Biologists Ltd.)

Competing Interests: Competing interests: Dr Moman is a member of the ASRA Resident Section Committee. Dr Moeschler is a Director at Large member of the North American Neuromodulation Society’s Board of Directors, and Board Member of the Association of Pain Program Directors. Dr Pearson is Chair for the ASRA Fall Annual Meeting 2022, President of Women in Anesthesiology, and Social Media Manager for the Anesthesia Patient Safety Foundation. Dr Hooten was Co-Director of the 2014 AAPM annual meeting and is currently President-Elect of AAPM.

Introduction: The introduction of successful neuromodulation strategies for managing chronic visceral pain lag behind what is now treatment of choice in refractory chronic back and extremity pain for many providers in the United States and Europe. Changes in public policy and monetary support to identify nonopioid treatments for chronic pain have sparked interest in alternative options. In this review, we discuss the scope of spinal cord stimulation (SCS) for visceral pain, its limitations, and the potential role for new intradural devices of the type that we are developing in our laboratories, which may be able to overcome existing challenges., Methods: A review of the available literature relevant to this topic was performed, with particular focus on the pertinent neuroanatomy and uses of spinal cord stimulation systems in the treatment of malignant and nonmalignant gastrointestinal, genitourinary, and chronic pelvic pain., Results: To date, there have been multiple off-label reports testing SCS for refractory gastrointestinal and genitourinary conditions. Though some findings have been favorable for these organs and systems, there is insufficient evidence to make this practice routine. The unique configuration and layout of the pelvic pain pathways may not be ideally treated using traditional SCS implantation techniques, and intradural stimulation may be a viable alternative., Conclusions: Despite the prevalence of visceral pain, the application of neuromodulation therapies, a standard approach for other painful conditions, has received far too little attention, despite promising outcomes from uncontrolled trials. Detailed descriptions of visceral pain pathways may offer several clues that could be used to implement devices tailored to this unique anatomy., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Chronic tissue injury was shown to induce progressive scarring in fibrotic diseases such as idiopathic pulmonary fibrosis (IPF), while an array of repair/regeneration and stress responses come to equilibrium to determine the outcome of injury at the organ level. In the lung, type I alveolar epithelial (ATI) cells constitute the epithelial barrier, while type II alveolar epithelial (ATII) cells play a pivotal role in regenerating the injured distal lungs. It had been demonstrated that eukaryotic cells possess repair machinery that can quickly patch the damaged plasma membrane after injury, and our previous studies discovered the membrane-mending role of Tripartite motif containing 72 (TRIM72) that expresses in a limited number of tissues including the lung. Nevertheless, the role of alveolar epithelial cell (AEC) repair in the pathogenesis of IPF has not been examined yet., Method: In this study, we tested the specific roles of TRIM72 in the repair of ATII cells and the development of lung fibrosis. The role of membrane repair was accessed by saponin assay on isolated primary ATII cells and rat ATII cell line. The anti-fibrotic potential of TRIM72 was tested with bleomycin-treated transgenic mice., Results: We showed that TRIM72 was upregulated following various injuries and in human IPF lungs. However, TRIM72 expression in ATII cells of the IPF lungs had aberrant subcellular localization. In vitro studies showed that TRIM72 repairs membrane injury of immortalized and primary ATIIs, leading to inhibition of stress-induced p53 activation and reduction in cell apoptosis. In vivo studies demonstrated that TRIM72 protects the integrity of the alveolar epithelial layer and reduces lung fibrosis., Conclusion: Our results suggest that TRIM72 protects injured lungs and ameliorates fibrosis through promoting post-injury repair of AECs.

Alveolar macrophages (AMs) guard the alveolar space of the lung. Phagocytosis by AMs plays a critical role in the defense against invading pathogens, the removal of dead cells or foreign particles, and in the resolution of inflammatory responses and tissue remodeling, processes that are mediated by various surface receptors of the AMs. Here, we report methods for the analysis of the phagocytic function of AMs using in vitro and in vivo assays and experimental strategies to differentiate between the pattern recognition receptor-, complement receptor-, and Fc gamma receptor-mediated phagocytosis. Finally, we discuss a method to establish and characterize a P. aeruginosa pneumonia model in mice to assess bacterial clearance in vivo. These assays represent the most common methods to evaluate AM functions and can also be used to study macrophage function and bacterial clearance in other organs.

Localized thickening of the basal portion of the ventricular septum or basal septal hypertrophy (BSH) has been identified both at autopsy and by imaging studies for decades; despite numerous investigations, there is no consensus on the significance of this finding and a remarkable lack of consistency in terminology. This paper summarizes the scientific literature on the topic, focusing on recent echocardiographic findings. A case description illustrating some of the complex issues involved in measurement and diagnosis and differentiation from sigmoidal hypertrophic cardiomyopathy (HCM) is presented. Criteria are proposed for diagnosing pathologic BSH which include the following: (1) Exertional symptoms compatible with left ventricular outflow tract obstruction (LVOTO) such as dyspnea, near-syncope, and chest discomfort; (2) Documented LVOTO gradient demonstrated at peak bicycle or post-treadmill exercise >30 mm Hg; and (3) Symptomatic improvement with β-blocker (or other negative inotropic) therapy (preferably accompanied by documentation of reduction of exercise-induced LVOT)., (© 2017, Wiley Periodicals, Inc.)

In this study, we have fabricated nanofuses from thin-film, arc-deposited carbon for use in permanent data storage. Thin-film carbon fuses have fewer fabrication barriers and retain the required resistivity and structural stability to act as a data-storage medium. Carbon thin films were characterized for their electrical, microstructural, and chemical bonding properties. Annealing these films in an argon environment at 400 °C reduced the resistivity from about 4 × 10 -2 Ω cm as deposited to about 5 × 10 -4 Ω cm, allowing a lower blowing voltage. Nanofuses with widths ranging from 200 to 60 nm were fabricated and tested. They blow with voltages between 2 and 5.5 V, and the nanofuses remain stable in both "1" and "0" states under a constantly applied read voltage of 1 V for over 90 h., Competing Interests: The authors declare no competing financial interest.

Objectives: Laryngopharyngeal reflux (LPR) is associated with inflammatory and neoplastic airway diseases. Gastric pepsin internalized by airway epithelial cells during reflux contributes to oxidative stress, inflammation, and carcinogenesis. Several plant extracts and compounds inhibit digestive enzymes and inflammatory or neoplastic changes to the esophagus in models of gastroesophageal reflux. This study examined the potential of chemoprotective phytochemicals to inhibit peptic activity and mitigate pepsin-mediated damage of airway epithelial cells., Methods: Cultured human laryngeal and hypopharyngeal epithelial cells were pretreated with curcumin (10 micromol/L), ecabet sodium (125 microg/mL), and anthocyanin-enriched black-raspberry extract (100 microg/mL) 30 minutes before treatment with pepsin (0.1 mg/mL; 1 hour; pH 7). Controls were treated with media pH 7 or pepsin pH 7 without phytochemicals. Cell damage and proliferative changes were assessed by electron microscopy, cell count, thymidine analog incorporation, and real-time polymerase chain reaction array. Pepsin inhibition was determined by in vitro kinetic assay., Results: Micromolar concentrations of curcumin, ecabet sodium, and black-raspberry extract inhibited peptic activity and pepsin-induced mitochondrial damage and hyperproliferation. Curcumin abrogated pepsin-mediated depression of tumor suppressor gene expression and altered the subcellular localization of pepsin following endocytosis., Conclusions: Several phytochemicals inhibit the pepsin-mediated cell damage underlying inflammatory or neoplastic manifestations of LPR. Dietary supplementation or adjunctive therapy with phytochemicals may represent novel preventive or therapeutic strategies for LPR-attributed disease.

We show the controllable patterning of palladium nanoparticles in both one and two dimensions using electron-beam lithography and reactive ion etching of a thin film of poly(acrylic acid) (PAA). After the initial patterning of the PAA, a monolayer of polystyrene-b-poly-2-vinylpyridine micelles is spun cast onto the surface. A short reactive ion etch is then used to transfer the micelle pattern into the patterned poly(acrylic acid). Finally, PdCl2 is loaded from solution into the patterned poly(acrylic acid) features, and a reactive-ion etching process is used to remove the remaining polymer and form Pd nanoparticles. This method yields location-controlled patches of nanoparticles, including single- and double-file lines and nanoparticle pairs. A locational accuracy of 9 nm or less in one direction was achieved by optimizing the size of the PAA features.

We have fabricated nanoscale fuses from CVD graphene sheets with a 'bow tie' geometry for write-once-read-many data storage applications. The fuses are programmed using thermal oxidation driven by Joule heating. Fuses that were 250 nm wide with 2.5 μm between contact pads were programmed with average voltages and powers of 4.9 V and 2.1 mW, respectively. The required voltages and powers decrease with decreasing fuse sizes. Graphene shows extreme chemical and electronic stability; fuses require temperatures of about 400 °C for oxidation, indicating that they are excellent candidates for permanent data storage. To further demonstrate this stability, fuses were subjected to applied biases in excess of typical read voltages; stable currents were observed when a voltage of 10 V was applied to the devices in the off state and 1 V in the on state for 90 h each.

This work demonstrates the use of a circuit-like DNA origami structure as a template to fabricate conductive gold and copper nanostructures on Si surfaces. We improved over previous results by using multiple Pd seeding steps to increase seed uniformity and density. Our process has also been characterized through atomic force microscopy, particle size distribution analysis, and scanning electron microscopy. We found that four successive Pd seeding steps yielded the best results for electroless metal plating on DNA origami. Electrical resistance measurements were done on both Au- and Cu-metallized nanostructures, with each showing ohmic behavior. Gold-plated DNA origami structures made under optimal conditions had an average resistivity of 7.0 × 10(-5) Ω·m, whereas copper-metallized structures had a resistivity as low as 3.6 × 10(-4) Ω·m. Importantly, this is the first demonstration of electrically conductive Cu nanostructures fabricated on either DNA or DNA origami templates. Although resistivities for both gold and copper samples were larger than those of the bulk metal, these metal nanostructures have the potential for use in electrically connecting small structures. In addition, these metallized objects might find use in surface-enhanced Raman scattering experiments.

DNA origami is a promising tool for use as a template in the design and fabrication of nanoscale structures. The ability to engineer selected staple strands on a DNA origami structure provides a high density of addressable locations across the structure. Here we report a method using site-specific attachment of gold nanoparticles to modified staple strands and subsequent metallization to fabricate conductive wires from DNA origami templates. We have modified DNA origami structures by lengthening each staple strand in select regions with a 10-base nucleotide sequence and have attached DNA-modified gold nanoparticles to the lengthened staple strands via complementary base-pairing. The high density of extended staple strands allowed the gold nanoparticles to pack tightly in the modified regions of the DNA origami, where the measured median gap size between neighboring particles was 4.1 nm. Gold metallization processes were optimized so that the attached gold nanoparticles grew until gaps between particles were filled and uniform continuous nanowires were formed. Finally, electron beam lithography was used to pattern electrodes in order to measure the electrical conductivity of metallized DNA origami, which showed an average resistance of 2.4 kΩ per metallized structure.

We have used block copolymer patterned arrays of 5 nm gold nanoparticles (AuNPs) for chemically aligned surface attachment of DNA origami. Addition of single-stranded DNA-thiol to AuNPs allowed a base paired attachment of sticky end modified DNA origami. Results indicate a stable, selective attachment between the DNA origami and ssDNA modified AuNPs. Yield data showed 74% of AuNP binding sites forming an attachment with a DNA origami rectangle, and control surfaces showed less than 0.5% nonspecific adsorption.

Background: Transarterial Chemoembolization (TACE) has been recognized as a successful way of managing symptomatic and/or progressive hepatic carcinoid metastases not amenable to surgical resection. Although it is a fairly safe procedure, it is not without its complications., Case Presentation: This is a case of a 53 year-old woman with a patent foramen ovale (PFO) and mild pulmonary hypertension who underwent TACE for progressive carcinoid liver metastases. She developed acute heart failure, due to a severe inflammatory response; this resulted in pneumatosis intestinalis due to non-occlusive mesenteric ischemia. We describe the successful non-operative management of her pneumatosis intestinalis and the role of a PFO in this patient's heart failure., Conclusion: TACE remains an effective and safe treatment for metastatic carcinoid not amenable to resection, this case illustrates the complexity of complications that can arise. A multi-disciplinary approach including ready access to advanced critical care facilities is recommended in managing such complex patients.

Rhabdom shedding in horseshoe crab lateral eye photoreceptors was studied with anti-opsin and anti-arrestin immunocytochemistry. Two, possibly three, distinct shedding mechanisms were revealed in animals maintained in natural lighting. Transient rhabdom shedding, triggered by dawn, is a brief, synchronous event that removes up to 10% of the rhabdom membrane. Whorls of rhabdomeral membrane break into vesicles and form compact multivesicular bodies. These debris particles are immunoreactive for opsin and are of a relatively uniform size, averaging approximately 2 microm(2) in area. Transient shedding requires that input from circadian efferent fibers to the retina precedes the light trigger, and cutting the optic nerve blocks efferent input and transient shedding. Light-driven rhabdom shedding is a progressive process. Rhabdomeral membrane is removed by coated vesicles that accumulate into loosely packed multivesicular bodies. These debris particles label with antibodies directed against opsin, arrestin, and adaptin, and they have a large distribution of sizes, averaging almost 6 microm(2) in area and ranging up to 25 microm(2) or more. The amount of rhabdomeral membrane removed by light-driven shedding has seasonal variation and depends on latitude. Light-driven shedding does not require circadian efferent input. A possible third shedding mechanism, light-independent shedding, is observed when transient shedding is blocked either by 48 hours of darkness or by cutting the optic nerve. Small particles, averaging 1.8 microm(2) in area, exhibiting opsin but not arrestin immunoreactivity can then be found in the cytoplasm surrounding the rhabdom. The nature of light-independent shedding is not yet clear., (Copyright 2002 Wiley-Liss, Inc.)

Background: Transesophageal echocardiography (TEE) is a useful procedure to evaluate selected stroke patients for cardiac sources of embolism. To date, noninfective valvular vegetations have not been described in large studies using transesophageal echocardiography to detect cardiac sources of embolism. We sought to investigate the frequency of noninfective valvular vegetations in patients with unexplained stroke referred for TEE and to determine the relationship of these vegetations to unrecognized thrombophilic disorders., Methods: We evaluated 641 consecutive patients referred for TEE as a result of unexplained stroke or transient ischemic attack for the presence of valvular vegetations. Of those with vegetations identified, serial blood cultures were obtained to evaluate for an infectious etiology. Patients also had serum testing for thrombophilic disorders and selected patients underwent cerebral angiography., Results: Thirteen patients (2%) who underwent TEE evaluation for unexplained stroke or transient ischemic attack were found to have noninfective valvular vegetations, all involving the mitral valve; none were identified by transthoracic echocardiography. Antiphospholipid antibodies were identified in 8 of these 13 patients (62%) and a protein C deficiency in 1 patient (8%)., Conclusions: Noninfective valvular vegetations are a potential cardiac source of embolism in patients with unexplained stroke that can be better identified using transesophageal echocardiography. A large percentage of these individuals have a previously unrecognized thrombophilic disorder.

Inhalation exposure to ozone (O3) is known to induce epithelial and inflammatory changes in the lungs, characterized by neutrophilia and changes in epithelial permeability. Several cell types and their soluble mediators, including interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha), are involved in the evolution of these responses. In this study, we have compared the effects of the combination of anti-IL-1 alpha and anti-TNF-alpha on in vitro and in vivo responses to inhaled O3. Male, Sprague-Dawley rats were exposed, nose-only, to 0.8 ppm O3 for 3 h and the in vitro and in vivo parameters were measured 8-12 h following exposure. The in vitro studies revealed that the adherence of inflammatory cells, primarily macrophages, harvested from the lungs of O3-exposed rats to cultured lung epithelial cells (ARL-14) was significantly greater than the adherence of macrophages from air-exposed controls. Furthermore, this adherence was significantly reduced in antibody-treated cells as compared to cells treated with preimmune rabbit serum. In vivo, elevations were found in the percentage of neutrophils in bronchoalveolar lavage fluid (BALF), transport of 99mTc-diethylenetriaminepentaacetate (DTPA) across the tracheal epithelium, and concentrations of total protein and albumin in BALF following O3 exposure. However, these effects were not significantly altered by treatment with the anti-IL-1 alpha/anti-TNF-alpha combination. Therefore, it was concluded that O3 affects the early stages of the inflammatory response, particularly with respect to macrophage activation and adherence to epithelial cells, and that this early response may be mediated by IL-1 alpha and/or TNF-alpha. The results also suggest that the in vivo effects of O3 are controlled by complex mechanisms involving factors other than IL-1 alpha and TNF-alpha, even though these cytokines are capable of modifying macrophage function as revealed by the in vitro adherence studies.

Background and Aims of the Study: Mitral valve prolapse due to floppy mitral valve (MVP/FMV) is a common valvular abnormality with a variable clinical course. Flail mitral valve leaflet resulting in severe mitral regurgitation is a complication of MVP/FMV., Methods: In order to understand the structural correlates of flail mitral valve leaflet in MVP, we reviewed the morphologic characteristics of the mitral valve by transesophageal echocardiography (TEE) in 72 patients (24 normal; 26 mitral valve prolapse; 22 flail mitral valve leaflet)., Results: Compared with the normal group, the mitral valve prolapse group had greater anterior and posterior mitral valve leaflet thickness and anterior mitral valve leaflet length. Patients with flail mitral valve leaflets as a complication of FMV had greater anterior and posterior mitral valve leaflet length and posterior mitral valve leaflet thickness compared with MVP patients without flail mitral valve leaflets. Posterior mitral valve leaflet length was the only echocardiographic independent predictor of flail mitral valve leaflet. Older FMV patients with increased mitral valve leaflet length and thickness are predisposed to flail mitral valve leaflets and severe mitral regurgitation., Conclusions: TEE may identify patients with MVP/FMV with the greatest structural abnormalities who are at risk for complications such as flail mitral valve leaflet(s).

The inflammatory response in the lungs following an inhalation exposure of animals and humans to ozone (O3) is associated with macrophage stimulation, release of chemotactic agents, and neutrophilia. This study investigated the adhesive behavior of the alveolar macrophages and its relevance to the inflammatory processes in the lung. Macrophages recovered by BAL from rats exposed to purified air or 0.8 ppm O3 were studied in vitro for their adhesion to epithelial cells derived from ARL-14. The macrophages from O3-exposed animals displayed greater adhesion to the epithelial cells than the macrophages from control rats exposed to purified air. The O3-induced adhesion was attenuated in the macrophages treated with a combination of interleukin-1 alpha and tumor necrosis factor-alpha antibodies (anti-IL-1+anti-TNF). The cell adhesion stimulated by O3 exposure was also attenuated when the macrophages were incubated in the presence of antibodies to leukocyte adhesion molecules, CD11b, or epithelial cell adhesion molecules, ICAM-1. A marginal increase in the surface expression of CD11b was noticed in macrophages from the rats exposed to O3. A similar change in the ICAM-1 expression was, however, not observed. The results suggest that the O3-induced modifications of macrophages are mediated by IL-1 and TNF, and that these modifications are accompanied by a minimal change in the expression of the cell-adhesion molecules.

The effects of hypertension on the arterial vasculature were examined in a study group of 20 patients with newly diagnosed essential hypertension, 18 patients with chronic essential hypertension, and 32 control subjects with normal blood pressure. Left ventricular mass was determined echocardiographically. Carotid artery intimal-medial thickness was measured by means of B-mode ultrasound imaging, and carotid arterial waveforms were obtained by applanation tonometry. Compared with that in control subjects, carotid intimal-medial thickness was increased in patients with chronic hypertension (0.74 +/- 0.17 mm vs 0.61 +/- 0.15 mm in control subjects; p < 0.01) and in patients with newly diagnosed hypertension (0.66 +/- 0.12 mm vs 0.61 +/- 0.15 mm in control subjects; p < 0.05). Left ventricular mass was also higher in patients with chronic hypertension than in control subjects but was very similar between control subjects and those with newly diagnosed hypertension. Both the group with early hypertension and the group with chronic hypertension had an increased incidence of early waveform reflection evident on carotid arterial waveform examination. By multiple regression analysis, independent predictors of increased carotid intimal-medial thickness were age, systolic arterial pressure, and Murgo class of arterial waveform. Conduit arterial wall thickening precedes left ventricular remodeling in essential hypertension and is significantly related to the degree of pressure elevation and the arterial waveform contour.

Posterior displacement of the mitral valve with billowing into the left atrium has been the major echocardiographic criterion used for the diagnosis of mitral valve prolapse (MVP). However, the current criteria are limited by the influence of hemodynamic factors on the degree of prolapse, whereas complications such as mitral regurgitation, endocarditis, and need for surgery have been associated with redundancy or thickening of the leaflets. Sixty-eight normal subjects (mean age, 40 years; range, 18 to 76 years) were compared with 58 patients with MVP (mean age, 37 years, range, 18 to 83 years). Leaflet displacement across the annular plane in the parasternal long-axis view was mandatory for the diagnosis of MVP. Transthoracic echocardiographic measurements of anterior and posterior leaflet thickness, leaflet length, and chordal length were made from the parasternal long-axis view and the mitral annular diameter, from the apical four-chamber and two-chamber views. The MVP group had greater anterior thickness (4.1 +/- 0.4 mm vs 5.3 +/- 0.7 mm; p = 0.0001), posterior thickness (3.2 +/- 0.4 mm vs 4.7 +/- 0.9 mm; p = 0.0001), anterior length (22.8 +/- 2.0 mm vs 25.7 +/- 1.7 mm; p = 0.0001), posterior length (12.8 +/- 1.0 mm vs 15.7 +/- 2.5 mm; p = 0.0001), chordal length (25.6 +/- 2.7 mm vs 28.0 +/- 2.5 mm; p = 0.0001), and annular diameter (29.1 +/- 1.5 mm vs 31.3 +/- 2.6 mm; p = 0.0001). Of the MVP group, >80% had at least one abnormality identified and >50% had at least two abnormalities. In addition, patients with MVP with significant regurgitation had greater anterior thickness (5.2 +/- 0.7 mm vs 5.8 +/- 0.8 mm; p = 0.015), posterior thickness (4.5 +/- 0.9 mm vs 5.3 +/- 0.7 mm; p = 0.024), posterior length (15.1 +/- 1.6 mm vs 17.9 +/- 4.2 mm; p = 0.004), and annular diameter (36.0 +/- 2.0 mm vs 33.3 +/- 2.1 mm; p = 0.0001). The majority of patients with floppy mitral valves resulting in MVP have structural abnormalities that may be defined by echocardiography. A spectrum of floppy valve structure is demonstrated by echocardiography, with mitral regurgitation occurring more frequently in patients with multiple and more severe anatomic abnormalities. In addition to the presence of prolapse and regurgitation, the assessment of leaflet thickness, leaflet length, annular diameter, and chordal length is fundamental to the definition and stratification of patients with MVP associated with the floppy mitral valve.

Background and Purpose: Filamentous strands attached to the mitral valve are a recently described finding in occasional patients undergoing transesophageal echocardiography (TEE), but the frequency and clinical significance of these strands remain poorly defined. The purpose of the present study was to review the prevalence of mitral valve strands in patients undergoing TEE examination and to explore the relation of these strands to cardioembolic cerebral ischemia., Methods: All patients with native mitral valves referred for clinically indicated TEE over a 2-year period at our institution were evaluated for the presence of mitral valve strands (defined as highly mobile filamentous masses <1 mm thick attached to the atrial surface of mitral leaflets)., Results: Of 968 study patients, mitral valve strands were identified in 22 individuals (2.3%). Mitral valve strands were significantly more common in patients referred for TEE as a result of a recent ischemic cerebrovascular event compared with patients referred for other study indications (6.3% versus 0.3%, respectively; P<.00001). Among patients < or = 50 years of age with likely cardioembolic stroke or transient ischemic attack, 16% were found to have mitral valve strands on TEE examination. In 9% of these young patients, no other TEE finding associated with cardioembolic risk was present., Conclusions: Filamentous strands attached to the mitral valve appear to represent another risk factor for embolic cerebral ischemia, particularly in patients < or = 50 years of age.

Early atherosclerotic changes in the carotid artery and thoracic aorta have been examined by high-frequency ultrasound measuring of intimal-medial thickness and stiffness. Whether changes in stiffness and thickness occur in parallel and whether the determinants of stiffness and thickness in the two vessels are similar is unknown. To examine the relation between ultrasonographic measures of atherosclerosis in the carotid and the thoracic aorta, 146 patients aged 20 to 84 years (mean 54 years) were studied by both transesophageal echocardiography (TEE) and carotid duplex scanning. From two-dimensionally derived M-mode recordings of the thoracic aorta and high-frequency B-mode imaging of the common carotid, the intimal-medial thickness was measured along with diastolic and systolic diameters for calculation of stiffness. Interobserver and intraobserver variability of carotid and aortic intimal-medial thickness and diameter were low. There was a good relation between carotid and aortic intimal-medial thickness (r = 0.69; p=0.0001). Age was the major independent determinant of thickness in both vessels. Carotid and aortic stiffness, as measured by Peterson's elastic modulus, were less closely related (r=0.51; p=0.0001). Age was the only independent predictor of stiffness in both vessels. In conclusion, structural ultrasonographic manifestations of early atherosclerosis in the carotid artery and thoracic aorta are closely related. Large population studies measuring only carotid intimal-medial two-thickness may reflect atherosclerotic changes occurring throughout the vascular bed.

The objective of this investigation was to determine the prevalence and clinical associations of systolic anterior motion (SAM) of the mitral chordae (chordal SAM) in patients without evidence of hypertrophic cardiomyopathy. Although SAM of the mitral valve is thought to be a specific marker of hypertrophic obstructive cardiomyopathy, little is known about the clinical significance of chordal SAM either as an isolated echocardiographic finding (ICSAM) or in patients with mitral valve prolapse (MVP). A retrospective search of the clinical echocardiographic database was made to identify studies demonstrating chordal SAM with no other echocardiographic features of hypertrophic cardiomyopathy. The prevalence of chordal SAM was also ascertained in a group of 97 normal control subjects. Clinical, demographic, and two-dimensional and Doppler echocardiographic characteristics were compared between patients with and without MVP. Chordal SAM was identified in 3.9 percent of clinical studies but was rarely seen in normal volunteers (1 percent). Of the 57 patients with chordal SAM, 21 had systemic or cardiovascular conditions other than MVP associated with SAM (including 7 with aortic insufficiency and 8 with secondary concentric left ventricular hypertrophy), 18 (32 percent) had MVP, and 19 (33 percent) had no associated cardiovascular or systemic condition. These 19 patients with ICSAM were similar to patients with MVP and SAM with respect to age (44 +/- 8 vs 41 +/- 17 years), blood pressure, left ventricular wall thickness, ejection fraction, left atrial size, degree of mitral insufficiency, and left ventricular outflow tract velocity. Indications for the echocardiographic studies were similar between the two groups (chest pain, syncope, arrhythmia, cardiac source of embolus, and suspected MVP), but more patients in the ICSAM group were men (16 of 19 vs 8 of 18; p < 0.05). In conclusion, patients with ICSAM and CSAM associated with MVP are virtually indistinguishable by clinical, demographic, or Doppler-echocardiographic features. The syndrome of ICSAM deserves further study as a potentially clinically significant echocardiographic variant of the floppy mitral valve/MVP syndrome.

Objectives: The purpose of this study was to determine how frequently prosthetic valve strands are associated with prosthetic mitral and aortic valves, as detected by transesophageal echocardiography, and to assess their significance in relation to clinical cardioembolic events., Background: Strands attached to prosthetic mitral valves are a recently described finding of uncertain clinical significance. There are no reports of strands attached to aortic valve prostheses, and data are limited concerning the relation of valvular strands to cardioembolic events., Methods: We identified all transesophageal echocardiographic studies performed during a 5-year period at our institution for evaluation of valve dysfunction or a suspected cardioembolic event in patients with a valve prosthesis. All studies were reviewed. The presence of strands was noted and the prevalence compared between patients evaluated for a suspected cardioembolic event and those evaluated for valve dysfunction. In patients with no strands detected, the presence of other potential cardiac sources of embolism was noted., Results: Strands were detected in 56 (26%) of 214 studies. There was a significant difference (p = 0.0001) in the prevalence of strands between studies performed for a suspected cardioembolic event (34 [53%] of 64) versus those performed for suspected valve dysfunction (22 [15%] of 150). Strands were more prevalent on mitral than on aortic valves (32% vs. 13%, p = 0.0004) and were more frequently detected on mechanical than on bioprosthetic valves (27% vs. 8%, p = 0.003). Among patients with a suspected cardioembolic event and normal valves, other potential cardiac sources of embolism were detected in 67%., Conclusions: Prosthetic valve strands are frequently detected by transesophageal echocardiography. They are more commonly detected in patients being evaluated for a suspected cardioembolic event and thus represent a potential cardiac source of embolism. In patients with apparently normal valves, other potential sources of embolism are frequently detected. Thus, transesophageal echo-cardiography may have a significant impact on the management of these patients.

Although it is well recognized that dobutamine is a powerful positive inotropic agent mediating increased myocardial contractility through direct beta-adrenergic stimulation, the mechanism of its overall circulatory effects appears more complex than that which may be ascribed solely to this direct action on the myocardium. Previous investigations have implied that reflex alterations in autonomic balance may contribute significantly to the response to this agent, but direct evidence describing such a response has not been reported. The objective of this investigation was to assess changes in autonomic tone induced by dobutamine in the presence and absence of ischemia through the measurement of heart rate variability in patients undergoing dobutamine stress echocardiography. Of 25 consecutive patients undergoing dobutamine stress echocardiography, 16 were found to have unequivocal evidence for or against the presence of ischemia during dobutamine infusion. Heart rate data from these 16 patients were submitted for spectral analysis of heart rate variability and quantification of parasympathetically governed high-frequency heart rate variability and sympathetically influenced low-frequency heart rate variability. Of the 16 patients nine were not found to have evidence for ischemia (group 1), and seven were found to have echocardiographic findings consistent with dobutamine-induced ischemia (group 2). The two groups significantly differed (p = 0.04) in the change in parasympathetic tone associated with dobutamine with a significant (p = 0.04) increase in parasympathetic tone in group 1 and a numeric decrease in group 2. A significant (p = 0.04) decrease in sympathetic tone was noted in group 1 as reflected by low-frequency heart rate variability with a numeric increase in this measure in group 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Multidimensional left atrial (LA) performance indices have not been extensively studied in chronic mitral valve disease. LA maximal volume, stroke volume (LA volume at atrial systole minus LA minimal volume), LA ejection fraction (stroke volume/volume at atrial systole) and A-wave velocity, were measured in 14 patients with mitral stenosis (mean mitral valve area 1.5 cm2); 14 patients with chronic mitral regurgitation all in sinus rhythm; and were compared to 20 age and sex matched normal control subjects using biplane transthoracic echo and pulsed Doppler. Although LA volumes--maximal and at onset of atrial systole--were greater in mitral regurgitation and mitral stenosis (p < 0.01) compared to normal subjects, LA ejection fraction was not statistically different among the three groups. LA stroke volume was greater in mitral regurgitation and mitral stenosis compared to normal subjects, p < 0.01. LA kinetic energy (LAKE) = 1/2 mv2 (m = LA stroke volume x 1.06, blood's specific gravity, v = A wave velocity) was increased in mitral stenosis and mitral regurgitation compared to normal subjects (p < 0.001). An inverse correlation (r = 0.66, p < 0.01) was present between LAKE and mitral valve area in mitral stenosis. It is concluded that LA function, a complex interplay of multiple factors, requires multidimensional methods of analysis beyond standard measurements of size and volume, which provide additional insight into normal LA function, and better definition of LA function changes involved in the natural history of chronic mitral valve disease.

We have demonstrated that the pulmonary venous and transmitral atrial duration, and the difference between the 2 are independent of age and not influenced by hypertension, but have a high interobserver variability and range of variability. Enthusiasm for this parameter with the currently available recording techniques must be tempered by the high variability in this measurement.