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https://www.readbyqxmd.com/read/28515954/a-prospective-cohort-study-of-thoracic-ultrasound-in-acute-respiratory-failure-the-c3po-protocol
#1
Peter D Wallbridge, Simon A Joosten, Liam M Hannan, Daniel P Steinfort, L Irving, J Goldin, Mark Hew
OBJECTIVES: This study was performed to assess the clinical utility of a standardised thoracic ultrasound examination when added to standard care in patients with acute respiratory failure admitted to an intermediate care unit. This study aimed to assess the impact on clinical diagnosis, clinician confidence and management. Ultrasound has been shown to have utility in patients admitted to intensive care and emergency; however, utility in a ward setting is unknown. DESIGN: Prospective cohort study...
May 2017: JRSM Open
https://www.readbyqxmd.com/read/28506090/rational-design-strategies-for-fimh-antagonists-new-drugs-on-the-horizon-for-urinary-tract-infection-and-crohn-s-disease
#2
Laurel K Mydock-McGrane, Thomas J Hannan, James W Janetka
The bacterial adhesin FimH is a virulence factor and an attractive therapeutic target for urinary tract infection (UTI) and Crohn's Disease (CD). Located on type 1 pili of uropathogenic E. coli (UPEC), the FimH adhesin plays an integral role in the pathogenesis of UPEC. Recent efforts have culminated in the development of small-molecule mannoside FimH antagonists that target the mannose-binding lectin domain of FimH, inhibiting its function and preventing UPEC from binding mannosylated host cells in the bladder, thereby circumventing infection...
May 16, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28500309/resveratrol-inhibits-release-of-soluble-fms-like-tyrosine-kinase-sflt-1-and-soluble-endoglin-and-improves-vascular-dysfunction-implications-as-a-preeclampsia-treatment
#3
Natalie J Hannan, Fiona C Brownfoot, Ping Cannon, Minh Deo, Sally Beard, Tuong V Nguyen, Kirsten R Palmer, Stephen Tong, Tu'uhevaha J Kaitu'u-Lino
Preeclampsia is a disease of pregnancy associated with placental oxidative stress, inflammation and elevated release of anti-angiogenic factors sFlt-1 and soluble endoglin. These placental factors cause generalized maternal endothelial dysfunction. There are no treatments to halt disease progression; delivery is the only cure. Resveratrol modulates pathways involved in inflammation and oxidative stress and may offer a potential therapeutic for preeclampsia. Resveratrol reduced sFlt-1, sFlt-1 e15a and soluble endoglin secretion from primary trophoblasts and HUVECs and reduced mRNA expression of pro-inflammatory molecules NFκB, IL-6 and IL-1β in trophoblasts...
May 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28482340/foot-function-foot-pain-and-falls-in-older-adults-the-framingham-foot-study
#4
Arunima Awale, Thomas J Hagedorn, Alyssa B Dufour, Hylton B Menz, Virginia A Casey, Marian T Hannan
BACKGROUND: Although foot pain has been linked to fall risk, contributions of pain severity, foot posture, or foot function are unclear. These factors were examined in a cohort of older adults. OBJECTIVE: The purpose of this study was to examine the associations of foot pain, severity of foot pain, and measures of foot posture and dynamic foot function with reported falls in a large, well-described cohort of older adults from the Framingham Foot Study. METHODS: Foot pain, posture, and function were collected from Framingham Foot Study participants who were queried about falls over the past year (0, 1, and ≥2 falls)...
May 9, 2017: Gerontology
https://www.readbyqxmd.com/read/28463242/exercise-alters-mouse-sperm-small-noncoding-rnas-and-induces-a-transgenerational-modification-of-male-offspring-conditioned-fear-and-anxiety
#5
A K Short, S Yeshurun, R Powell, V M Perreau, A Fox, J H Kim, T Y Pang, A J Hannan
There is growing evidence that the preconceptual lifestyle and other environmental exposures of a father can significantly alter the physiological and behavioral phenotypes of their children. We and others have shown that paternal preconception stress, regardless of whether the stress was experienced during early-life or adulthood, results in offspring with altered anxiety and depression-related behaviors, attributed to hypothalamic-pituitary-adrenal axis dysregulation. The transgenerational response to paternal preconceptual stress is believed to be mediated by sperm-borne small noncoding RNAs, specifically microRNAs...
May 2, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28454825/incomplete-revascularization-for-percutaneous-coronary-interventions-variation-among-operators-and-association-with-operator-and-hospital-characteristics
#6
Edward L Hannan, Ye Zhong, Alice K Jacobs, Frederick S K Ling, Peter B Berger, Gary Walford, Ferdinand J Venditti, Spencer B King
BACKGROUND: Many studies have compared outcomes for incomplete revascularization (IR) among patients undergoing percutaneous coronary interventions (PCIs), but little is known about the correlates of IR, the extent to which complete revascularization (CR) was attempted unsuccessfully, and the variation across operators in the use of IR. METHODS: New York's PCI registry was used to examine medium-term mortality for IR, the variables associated with the use of IR, and the variation across operators in the utilization of IR after controlling for patient factors...
April 2017: American Heart Journal
https://www.readbyqxmd.com/read/28451393/the-circulating-microrna-200-family-in-whole-blood-are-potential-biomarkers-for-high-grade-serous-epithelial-ovarian-cancer
#7
Adam Pendlebury, Natalie J Hannan, Natalie Binder, Sally Beard, Monica Mcgauran, Peter Grant, Stephen Tong, Clare L Whitehead
Epithelial ovarian cancer (EOC) is the leading cause of mortality with regard to gynaecological cancer. There is no effective biomarker and therefore prognosis is poor as the majority of cases are not diagnosed until advanced disease is present. MicroRNAs (miRs) are dysregulated in ovarian cancer tissue and are present in the circulation. The aim of the present study was to investigate whether circulating miRs from the miR-200 family served as potential candidate biomarkers for the early detection of EOC. Whole blood and ovarian tissue were collected from women with early (stage I/II, n=4), advanced EOC (stage III/IV, n=4), and women with benign ovarian masses (n=5)...
March 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28416734/the-angiotensin-receptor-blocker-losartan-inhibits-mammary-tumor-development-and-progression-to-invasive-carcinoma
#8
Rhiannon Coulson, Seng H Liew, Angela A Connelly, Nicholas S Yee, Siddhartha Deb, Beena Kumar, Ana C Vargas, Sandra A O'Toole, Adam C Parslow, Ashleigh Poh, Tracy Putoczki, Riley J Morrow, Mariah Alorro, Kyren A Lazarus, Evie F W Yeap, Kelly L Walton, Craig A Harrison, Natalie J Hannan, Amee J George, Colin D Clyne, Matthias Ernst, Andrew M Allen, Ashwini L Chand
Drugs that target the Renin-Angiotensin System (RAS) have recently come into focus for their potential utility as cancer treatments. The use of Angiotensin Receptor Blockers (ARBs) and Angiotensin-Converting Enzyme (ACE) Inhibitors (ACEIs) to manage hypertension in cancer patients is correlated with improved survival outcomes for renal, prostate, breast and small cell lung cancer. Previous studies demonstrate that the Angiotensin Receptor Type I (AT1R) is linked to breast cancer pathogenesis, with unbiased analysis of gene-expression studies identifying significant up-regulation of AGTR1, the gene encoding AT1R in ER+ve/HER2-ve tumors correlating with poor prognosis...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28399716/the-lgbtqi-health-forum-an-innovative-interprofessional-initiative-to-support-curriculum-reform
#9
Hannan M Braun, David Ramirez, Greg J Zahner, Eva Mae Gillis-Buck, Heather Sheriff, Marcus Ferrone
Lesbian, gay, bisexual, transgender, queer, and intersex (LGBTQI) individuals continue to face barriers to accessing appropriate and comprehensive healthcare. Compounding this problem, healthcare trainees report few training opportunities and low levels of preparedness to care for LGBTQI patients. In 2009, an interprofessional group of students and a faculty advisor at the University of California, San Francisco, developed a novel student-organized LGBTQI Health Forum for medical, dental, pharmacy, nursing, and physical therapy students to deliver LGBTQI health content that was otherwise absent from the formal curriculum...
2017: Medical Education Online
https://www.readbyqxmd.com/read/28379296/relaxin-treatment-reduces-angiotensin-ii-induced-vasoconstriction-in-pregnancy-and-protects-against-endothelial-dysfunction%C3%A2
#10
Sarah A Marshall, Chen Huei Leo, Jane E Girling, Marianne Tare, Sally Beard, Natalie J Hannan, Laura J Parry
The peptide relaxin has gained considerable attention as a new vasoactive drug, largely through its beneficial therapeutic effects in cardiovascular disease. In this study, we tested the hypothesis that relaxin treatment alleviates systemic vascular dysfunction characteristic of hypertensive diseases of pregnancy. We investigated vascular effects and mechanisms of relaxin action in (i) pregnant relaxin-deficient (Rln-/-) mice with enhanced responses to angiotensin II (AngII) and (ii) arteries pre-incubated ex vivo in trophoblast conditioned media (TCM) to induce endothelial dysfunction...
April 1, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28377290/synaptopathic-mechanisms-of-neurodegeneration-and-dementia-insights-from-huntington-s-disease
#11
REVIEW
Shiraz Tyebji, Anthony J Hannan
Dementia encapsulates a set of symptoms that include loss of mental abilities such as memory, problem solving or language, and reduces a person's ability to perform daily activities. Alzheimer's disease is the most common form of dementia, however dementia can also occur in other neurological disorders such as Huntington's disease (HD). Many studies have demonstrated that loss of neuronal cell function manifests pre-symptomatically and thus is a relevant therapeutic target to alleviate symptoms. Synaptopathy, the physiological dysfunction of synapses, is now being approached as the target for many neurological and psychiatric disorders, including HD...
April 2, 2017: Progress in Neurobiology
https://www.readbyqxmd.com/read/28330863/bacterial-virulence-phenotypes-of-escherichia-coli-and-host-susceptibility-determine-risk-for-urinary-tract-infections
#12
Henry L Schreiber, Matt S Conover, Wen-Chi Chou, Michael E Hibbing, Abigail L Manson, Karen W Dodson, Thomas J Hannan, Pacita L Roberts, Ann E Stapleton, Thomas M Hooton, Jonathan Livny, Ashlee M Earl, Scott J Hultgren
Urinary tract infections (UTIs) are caused by uropathogenic Escherichia coli (UPEC) strains. In contrast to many enteric E. coli pathogroups, no genetic signature has been identified for UPEC strains. We conducted a high-resolution comparative genomic study using E. coli isolates collected from the urine of women suffering from frequent recurrent UTIs. These isolates were genetically diverse and varied in their urovirulence, that is, their ability to infect the bladder in a mouse model of cystitis. We found no set of genes, including previously defined putative urovirulence factors (PUFs), that were predictive of urovirulence...
March 22, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28326313/lung-volume-recruitment-acutely-increases-respiratory-system-compliance-in-individuals-with-severe-respiratory-muscle-weakness
#13
Yannick Molgat-Seon, Liam M Hannan, Paolo B Dominelli, Carli M Peters, Renee J Fougere, Douglas A McKim, A William Sheel, Jeremy D Road
The aim of the present study was to determine whether lung volume recruitment (LVR) acutely increases respiratory system compliance (Crs) in individuals with severe respiratory muscle weakness (RMW). Individuals with RMW resulting from neuromuscular disease or quadriplegia (n=12) and healthy controls (n=12) underwent pulmonary function testing and the measurement of Crs at baseline, immediately after, 1 h after and 2 h after a single standardised session of LVR. The LVR session involved 10 consecutive supramaximal lung inflations with a manual resuscitation bag to the highest tolerable mouth pressure or a maximum of 50 cmH2O...
January 2017: ERJ Open Research
https://www.readbyqxmd.com/read/28292463/key-players-of-the-necroptosis-pathway-ripk1-and-sirt2-are-altered-in-placenta-from-preeclampsia-and-fetal-growth-restriction
#14
Natalie J Hannan, Sally Beard, Natalie K Binder, Kenji Onda, Tu'uhevaha J Kaitu'u-Lino, Qi Chen, Laura Tuohey, Manarangi De Silva, Stephen Tong
INTRODUCTION: Preeclampsia (PE) and fetal growth restriction (FGR) are among the leading causes of perinatal morbidity and mortality. Placental insufficiency is central to these conditions. The mechanisms underlying placental insufficiency are poorly understood. Apoptosis has long been considered the only form of regulated cell death, recent research has identified an alternate process of programmed cell death known as necroptosis [1]. Necroptosis is distinct from apoptosis, relying on the deacetylase sirtuin-2 [2], receptor interacting kinases RIPK1 and 3, and the pseudokinase MLKL [3]...
March 2017: Placenta
https://www.readbyqxmd.com/read/28283481/inhibition-of-pol-i-transcription-treats-murine-and-human-aml-by-targeting-the-leukemia-initiating-cell-population
#15
Nadine Hein, Donald P Cameron, Katherine M Hannan, Nhu-Y N Nguyen, Chun Yew Fong, Jirawas Sornkom, Meaghan Wall, Megan Pavy, Carleen Cullinane, Jeannine Diesch, Jennifer R Devlin, Amee J George, Elaine Sanij, Jaclyn Quin, Gretchen Poortinga, Inge Verbrugge, Adele Baker, Denis Drygin, Simon J Harrison, James D Rozario, Jason A Powell, Stuart M Pitson, Johannes Zuber, Ricky W Johnstone, Mark A Dawson, Mark A Guthridge, Andrew Wei, Grant A McArthur, Richard B Pearson, Ross D Hannan
Despite the development of novel drugs, prospects for many patients with acute myeloid leukemia (AML) remain dismal. This study reveals that the selective inhibitor of RNA Polymerase I (Pol I) transcription, CX-5461, effectively treats aggressive AML, including MLL-driven AML, and outperforms standard chemotherapies. In addition to the previously characterized mechanism of action of CX-5461, the induction of p53-dependant apoptotic cell death, inhibition of Pol I transcription also demonstrates potent efficacy in p53null AML in vivo...
March 10, 2017: Blood
https://www.readbyqxmd.com/read/28279289/changes-in-percutaneous-coronary-interventions-deemed-inappropriate-by%C3%A2-appropriate-use-criteria
#16
Edward L Hannan, Zaza Samadashvili, Kimberly Cozzens, Foster Gesten, Alda Osinaga, Douglas G Fish, Constance L Donahue, Ronald J Bass, Gary Walford, Alice K Jacobs, Ferdinand J Venditti, Nicholas J Stamato, Peter B Berger, Samin Sharma, Spencer B King
BACKGROUND: Recent studies have demonstrated relatively high rates of percutaneous coronary interventions (PCIs) classified as "inappropriate." The New York State Department of Health shared rates with hospitals and announced the intention of withholding reimbursement pending demonstration of clinical rationale for Medicaid patients with inappropriate PCIs. OBJECTIVES: The objective was to examine changes over time in the number and rate of inappropriate PCIs. METHODS: Appropriate use criteria were applied to PCIs performed in New York in patients without acute coronary syndromes or previous coronary artery bypass graft surgery in periods before (2010 through 2011) and after (2012 through 2014) efforts were made to decrease inappropriateness rates...
March 14, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/28262675/genomic-characterisation-of-e%C3%AE-myc-mouse-lymphomas-identifies-bcor-as-a-myc-co-operative-tumour-suppressor-gene
#17
Marcus Lefebure, Richard W Tothill, Elizabeth Kruse, Edwin D Hawkins, Jake Shortt, Geoffrey M Matthews, Gareth P Gregory, Benjamin P Martin, Madison J Kelly, Izabela Todorovski, Maria A Doyle, Richard Lupat, Jason Li, Jan Schroeder, Meaghan Wall, Stuart Craig, Gretchen Poortinga, Don Cameron, Megan Bywater, Lev Kats, Micah D Gearhart, Vivian J Bardwell, Ross A Dickins, Ross D Hannan, Anthony T Papenfuss, Ricky W Johnstone
The Eμ-Myc mouse is an extensively used model of MYC driven malignancy; however to date there has only been partial characterization of MYC co-operative mutations leading to spontaneous lymphomagenesis. Here we sequence spontaneously arising Eμ-Myc lymphomas to define transgene architecture, somatic mutations, and structural alterations. We identify frequent disruptive mutations in the PRC1-like component and BCL6-corepressor gene Bcor. Moreover, we find unexpected concomitant multigenic lesions involving Cdkn2a loss and other cancer genes including Nras, Kras and Bcor...
March 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/28255744/framing-of-mobility-items-a-source-of-poor-agreement-between-preference-based-health-related-quality-of-life-instruments-in-a-population-of-individuals-receiving-assisted-ventilation
#18
Liam M Hannan, David G T Whitehurst, Stirling Bryan, Jeremy D Road, Christine F McDonald, David J Berlowitz, Mark E Howard
PURPOSE: To explore the influence of descriptive differences in items evaluating mobility on index scores generated from two generic preference-based health-related quality of life (HRQoL) instruments. METHODS: The study examined cross-sectional data from a postal survey of individuals receiving assisted ventilation in two state/province-wide home mechanical ventilation services, one in British Columbia, Canada and the other in Victoria, Australia. The Assessment of Quality of Life 8-dimension (AQoL-8D) and the EQ-5D-5L were included in the data collection...
June 2017: Quality of Life Research
https://www.readbyqxmd.com/read/28255463/social-isolation-alters-social-and-mating-behavior-in-the-r451c-neuroligin-mouse-model-of-autism
#19
E L Burrows, A F Eastwood, C May, S C Kolbe, T Hill, N M McLachlan, L Churilov, A J Hannan
Autism spectrum disorder (ASD) is a neurodevelopmental disorder typified by impaired social communication and restrictive and repetitive behaviors. Mice serve as an ideal candidate organism for studying the neural mechanisms that subserve these symptoms. The Neuroligin-3 (NL3) mouse, expressing a R451C mutation discovered in two Swedish brothers with ASD, exhibits impaired social interactions and heightened aggressive behavior towards male mice. Social interactions with female mice have not been characterized and in the present study were assessed in male NL3(R451C) and WT mice...
2017: Neural Plasticity
https://www.readbyqxmd.com/read/28246638/evolutionary-fine-tuning-of-conformational-ensembles-in-fimh-during-host-pathogen-interactions
#20
Vasilios Kalas, Jerome S Pinkner, Thomas J Hannan, Michael E Hibbing, Karen W Dodson, Alex S Holehouse, Hao Zhang, Niraj H Tolia, Michael L Gross, Rohit V Pappu, James Janetka, Scott J Hultgren
Positive selection in the two-domain type 1 pilus adhesin FimH enhances Escherichia coli fitness in urinary tract infection (UTI). We report a comprehensive atomic-level view of FimH in two-state conformational ensembles in solution, composed of one low-affinity tense (T) and multiple high-affinity relaxed (R) conformations. Positively selected residues allosterically modulate the equilibrium between these two conformational states, each of which engages mannose through distinct binding orientations. A FimH variant that only adopts the R state is severely attenuated early in a mouse model of uncomplicated UTI but is proficient at colonizing catheterized bladders in vivo or bladder transitional-like epithelial cells in vitro...
February 2017: Science Advances
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