Medicine and Health Sciences Commons^™

A Ventilator Strategy Combining Low Tidal Volume Ventilation, Recruitment Maneuvers, And High Positive End-Expiratory Pressure Does Not Increase Sedative, Opioid, Or Neuromuscular Blocker Use In Adults With Acute Respiratory Distress Syndrome And May Improve Patient Comfort, Sangeeta Mehta, Deborah J. Cook, Yoanna Skrobik, John Muscedere

Anatomy and Cell Biology Publications

Background: The Lung Open Ventilation Study (LOV Study) compared a low tidal volume strategy with an experimental strategy combining low tidal volume, lung recruitment maneuvers, and higher plateau and positive end-expiratory pressures (PEEP) in adults with acute respiratory distress syndrome (ARDS). Herein, we compared sedative, opioid, and neuromuscular blocker (NMB) use among patients managed with the intervention and control strategies and clinicians' assessment of comfort in both groups. Methods: This was an observational substudy of the LOV Study, a randomized trial conducted in 30 intensive care units in Canada, Australia, and Saudi Arabia. In 16 centers, we recorded daily doses …

Induction Of Acute Lung Inflammation In Mice With Hemorrhagic Shock And Resuscitation: Role Of Hmgb1, Raymond L. C. Kao, Xuemei Xu, Anargyros Xenocostas, Neil Parry, Tina Mele, Claudio M. Martin, Tao Rui

Anatomy and Cell Biology Publications

Background: Hemorrhagic shock and resuscitation (HS/R) can induce multiple organ failure which is associated with high mortality. The lung is an organ commonly affected by the HS/R. Acute lung injury is a major cause of dysfunction in other organ systems. The objective of this study is to test the hypothesis that HS/R causes increased gut permeability which results in induction of high mobility group box1 protein (HMGB1) and further leads to the development of acute lung inflammation. Materials and methods: A mouse model of HS/R was employed in this study. Gut permeability and bacterial translocation were assessed with circulating FD4 …

Unique Functional Abnormalities In Youth With Combined Marijuana Use And Depression: An Fmri Study, Kristen A. Ford, Michael Wammes, Richard W. Neufeld, Derek Mitchell, Jean Theberge, Peter Williamson, Elizabeth A. Osuch

Anatomy and Cell Biology Publications

Prior research has shown a relationship between early onset marijuana (MJ) use and depression; however, this relationship is complex and poorly understood. Here, we utilized passive music listening and fMRI to examine functional brain activation to a rewarding stimulus in 75 participants [healthy controls (HC), patients with major depressive disorder (MDD), frequent MJ users, and the combination of MDD and MJ (MDD?+?MJ)]. For each participant, a preferred and neutral piece of instrumental music was determined (utilizing ratings on a standardized scale), and each completed two 6-min fMRI scans of a passive music listening task. Data underwent pre-processing and 61 participants …

Cardiac Fibroblasts Contribute To Myocardial Dysfunction In Mice With Sepsis: The Role Of Nlrp3 Inflammasome Activation, Wenbo Zhang, Xuemei Xu, Raymond Kao, Tina Mele, Peter Kvietys, Claudio M. Martin, Tao Rui

Anatomy and Cell Biology Publications

Myocardial contractile dysfunction in sepsis is associated with the increased morbidity and mortality. Although the underlying mechanisms of the cardiac depression have not been fully elucidated, an exaggerated inflammatory response is believed to be responsible. Nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome is an intracellular platform that is involved in the maturation and release of interleukin (IL)-1 beta. The aim of the present study is to evaluate whether sepsis activates NLRP3 inflammasome/caspase-1/IL-1 beta pathway in cardiac fibroblasts (CFs) and whether this cytokine can subsequently impact the function of cardiomyocytes (cardiac fibroblast-myocyte crosstalk). We show that treatment of …

Comparing Moral Judgments Of Patients With Frontotemporal Dementia And Frontal Stroke, Sandra Baez, Blas Couto, Teresa Torralva, Luciano A. Sposato, David Huepe, Patricia Montañes, Pablo Reyes, Diana Matallana, Nora S. Vigliecca, Andrea Slachevsky, Facundo Manes, Agustin Ibanez

Anatomy and Cell Biology Publications

Importance Several clinical reports have stated that patients with prefrontal lesions or patients with the behavioral variant of frontotemporal dementia share social cognition impairments. Moral reasoning is impaired in both conditions but there have been few investigations that directly compare this domain in the 2 groups.

Observations This work compared the moral judgments of these patient groups using a task designed to disentangle the contributions of intentions and outcomes in moral judgment. For both disorders, patients judged scenarios where the protagonists believed that they would cause harm but did not as being more permissible than the control group. Moreover, patients …

Complexity And Familiarity Enhance Single-Trial Detectability Of Imagined Movements With Electroencephalography, Raechelle M. Gibson, Srivas Chennu, Adrian M. Owen, Damian Cruse

Anatomy and Cell Biology Publications

Objective: We sought to determine whether the sensorimotor rhythms (SMR) elicited during motor imagery (MI) of complex and familiar actions could be more reliably detected with electroencephalography (EEG), and subsequently classified on a single-trial basis, than those elicited during relatively simpler imagined actions. Methods: Groups of healthy volunteers, including experienced pianists and ice hockey players, performed MI of varying complexity and familiarity. Their electroencephalograms were recorded and compared using brain-computer interface (BCI) approaches and spectral analyses. Results: Relative to simple MI, significantly more participants produced classifiable SMR for complex MI. During MI of performance of a complex musical piece, the …

Cholinergic Signaling Exerts Protective Effects In Models Of Sympathetic Hyperactivity-Induced Cardiac Dysfunction, Mariana Gavioli, Aline Lara, Pedro W. M. Almeida, Augusto Martins Lima, Denis D. Damasceno, Cibele Rocha-Resende, Marina Ladeira, Rodrigo R. Resende, Patricia M. Martinelli, Marcos Barrouin Melo, Patricia C. Brum, Marco Antonio Peliky Fontes, Robson A. Souza Santos, Marco A. M. Prado, Silvia Guatimosim

Anatomy and Cell Biology Publications

Cholinergic control of the heart is exerted by two distinct branches; the autonomic component represented by the parasympathetic nervous system, and the recently described non-neuronal cardiomyocyte cholinergic machinery. Previous evidence has shown that reduced cholinergic function leads to deleterious effects on the myocardium. Yet, whether conditions of increased cholinergic signaling can offset the pathological remodeling induced by sympathetic hyperactivity, and its consequences for these two cholinergic axes are unknown. Here, we investigated two models of sympathetic hyperactivity: i) the chronic beta-adrenergic receptor stimulation evoked by isoproterenol (ISO), and ii) the alpha(2A)/alpha(2C)-drenergic receptor knockout (KO) mice that lack pre-synaptic adrenergic receptors. …

The Neural Correlates Of Regulating Positive And Negative Emotions In Medication-Free Major Depression, Steven G. Greening, Elizabeth A. Osuch, Peter C. Williamson, Derek G. V. Mitchell

Anatomy and Cell Biology Publications

Depressive cognitive schemas play an important role in the emergence and persistence of major depressive disorder (MDD). The current study adapted emotion regulation techniques to reflect elements of cognitive behavioural therapy (CBT) and related psychotherapies to delineate neurocognitive abnormalities associated with modulating the negative cognitive style in MDD. Nineteen non-medicated patients with MDD and 19 matched controls reduced negative or enhanced positive feelings elicited by emotional scenes while undergoing functional magnetic resonance imaging. Although both groups showed significant emotion regulation success as measured by subjective ratings of affect, the controls were significantly better at modulating both negative and positive emotion. …

Skin Disease And Non-Syndromic Hearing Loss-Linked Cx30 Mutations Exhibit Several Distinct Cellular Pathologies, Amy Berger, John Kelly, Patrick Lajoie, Qing Shao, Dale Laird

Anatomy and Cell Biology Publications

Connexin 30 (Cx30), a member of the large gap junction protein family, plays a role in the homeostasis of the epidermis and inner ear through gap junctional intercellular communication (GJIC). Here, we investigated the underlying mechanisms of four autosomal dominant Cx30 gene mutations linked to hearing loss and/or various skin diseases. First, the T5M mutant linked to non-syndromic hearing loss formed functional gap junction channels and hemichannels, similar to wild type Cx30. The loss-of-function V37E mutant associated with Clouston syndrome or keratitis-ichthyosis-deafness syndrome was retained in the endoplasmic reticulum and significantly induced apoptosis. The G59R mutant linked to Vohwinkel and …

Recent Advances In The Molecular Characterization Of Circulating Tumor Cells, Lori E. Lowes, Alison L. Allan

Anatomy and Cell Biology Publications

Although circulating tumor cells (CTCs) were first observed over a century ago, lack of sensitive methodology precluded detailed study of these cells until recently. However, technological advances have now facilitated the identification, enumeration, and characterization of CTCs using a variety of methods. The majority of evidence supporting the use of CTCs in clinical decision-making has been related to enumeration using the CellSearch((R)) system and correlation with prognosis. Growing evidence also suggests that CTC monitoring can provide an early indication of patient treatment response based on comparison of CTC levels before and after therapy. However, perhaps the greatest potential that CTCs …

Adaptation Of Semiautomated Circulating Tumor Cell (Ctc) Assays For Clinical And Preclinical Research Applications, Lori E. Lowes, Benjamin D. Hedley, Michael Keeney, Alison L. Allan

Anatomy and Cell Biology Publications

The majority of cancer-related deaths occur subsequent to the development of metastatic disease. This highly lethal disease stage is associated with the presence of circulating tumor cells (CTCs). These rare cells have been demonstrated to be of clinical significance in metastatic breast, prostate, and colorectal cancers. The current gold standard in clinical CTC detection and enumeration is the FDA-cleared CellSearch system (CSS). This manuscript outlines the standard protocol utilized by this platform as well as two additional adapted protocols that describe the detailed process of user-defined marker optimization for protein characterization of patient CTCs and a comparable protocol for CTC …

Activation Of Mglur2/3 Receptors In The Ventral Prefrontal Cortex Reverses Sensorimotor Gating Deficits Induced By A Systemic Nmda Receptor Antagonist, Bridget Valsamis, Michael Chang, Marei Typlt, Susanne Schmid

Anatomy and Cell Biology Publications

Prepulse inhibition (PPI) of acoustic startle is an operational measure of sensorimotor gating, which is disrupted in schizophrenia. NMDA receptor (NMDAR) antagonist induced PPI disruption has become an important pharmacological model for schizophrenia; however, knowledge of the underlying mechanism remains incomplete. This study examines the role of NMDAR in the caudal pontine reticular nucleus (PnC) and the medial prefrontal cortex (mPFC) in NMDARs antagonist induced PPI deficits, as well as the NMDA receptor subtypes involved. We administered the NMDA antagonist MK-801 locally into the caudal pontine reticular formation (PnC), where the PPI mediating pathway converges with the primary startle pathway, …