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https://www.readbyqxmd.com/read/28416734/the-angiotensin-receptor-blocker-losartan-inhibits-mammary-tumor-development-and-progression-to-invasive-carcinoma
#1
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
#2
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
#3
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 3, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28377290/synaptopathic-mechanisms-of-neurodegeneration-and-dementia-insights-from-huntington-s-disease
#4
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 1, 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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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...
March 2, 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
#12
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
#13
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
https://www.readbyqxmd.com/read/28212321/therapeutic-approaches-targeting-myc-driven-prostate-cancer
#14
REVIEW
Richard J Rebello, Richard B Pearson, Ross D Hannan, Luc Furic
The transcript encoding the proto-oncogene MYC is commonly overexpressed in prostate cancer (PC). MYC protein abundance is also increased in the majority of cases of advanced and metastatic castrate-resistant PC (mCRPC). Accordingly, the MYC-directed transcriptional program directly contributes to PC by upregulating the expression of a number of pro-tumorigenic factors involved in cell growth and proliferation. A key cellular process downstream of MYC activity is the regulation of ribosome biogenesis which sustains tumor growth...
February 16, 2017: Genes
https://www.readbyqxmd.com/read/28196627/environmental-enrichment-enhances-cognitive-flexibility-in-c57bl-6-mice-on-a-touchscreen-reversal-learning-task
#15
Ariel Zeleznikow-Johnston, Emma L Burrows, Thibault Renoir, Anthony J Hannan
Environmental enrichment (EE) is any positive modification of the 'standard housing' (SH) conditions in which laboratory animals are typically held, usually involving increased opportunity for cognitive stimulation and physical activity. EE has been reported to enhance baseline performance of wild-type animals on traditional cognitive behavioural tasks. Recently, touchscreen operant testing chambers have emerged as a way of performing rodent cognitive assays, providing greater reproducibility, translatability and automatability...
February 11, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28194447/g%C3%AE-11-mutation-in-mice-causes-hypocalcemia-rectifiable-by-calcilytic-therapy
#16
Caroline M Gorvin, Fadil M Hannan, Sarah A Howles, Valerie N Babinsky, Sian E Piret, Angela Rogers, Andrew J Freidin, Michelle Stewart, Anju Paudyal, Tertius A Hough, M Andrew Nesbit, Sara Wells, Tonia L Vincent, Stephen D M Brown, Roger D Cox, Rajesh V Thakker
Heterozygous germline gain-of-function mutations of G-protein subunit α11 (Gα11), a signaling partner for the calcium-sensing receptor (CaSR), result in autosomal dominant hypocalcemia type 2 (ADH2). ADH2 may cause symptomatic hypocalcemia with low circulating parathyroid hormone (PTH) concentrations. Effective therapies for ADH2 are currently not available, and a mouse model for ADH2 would help in assessment of potential therapies. We hypothesized that a previously reported dark skin mouse mutant (Dsk7) - which has a germline hypermorphic Gα11 mutation, Ile62Val - may be a model for ADH2 and allow evaluation of calcilytics, which are CaSR negative allosteric modulators, as a targeted therapy for this disorder...
February 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28183462/the-impact-of-excluding-shock-patients-on%C3%A2-hospital-and-physician-risk-adjusted-mortality-rates-for-percutaneous-coronary%C3%A2-interventions-the-implications-for-public-reporting
#17
Edward L Hannan, Ye Zhong, Kimberly Cozzens, Foster Gesten, Marcus Friedrich, Peter B Berger, Alice K Jacobs, Gary Walford, Frederick S K Ling, Ferdinand J Venditti, Spencer B King
OBJECTIVES: The authors examined the impact of including shock patients in public reporting of percutaneous coronary intervention (PCI) risk-adjusted mortality. BACKGROUND: There is concern that an unintended consequence of statewide public reporting of medical outcomes is the avoidance of appropriate interventions for high-risk patients. METHODS: New York State's PCI registry was used to compare hospital and physician risk-adjusted mortality rates and outliers from New York's public report models with rates and outliers based on statistical models that include refractory shock patients and exclude both refractory shock and other shock patients...
February 13, 2017: JACC. Cardiovascular Interventions
https://www.readbyqxmd.com/read/28161077/m1-macrophages-are-predominantly-recruited-to-the-major-pelvic-ganglion-of-the-rat-following-cavernous-nerve-injury
#18
Hotaka Matsui, Nikolai A Sopko, Johanna L Hannan, Allison A Reinhardt, Max Kates, Takahiro Yoshida, Xiaopu Liu, Fabio Castiglione, Petter Hedlund, Emmanuel Weyne, Maarten Albersen, Trinity J Bivalacqua
INTRODUCTION: Neurogenic erectile dysfunction is a common sequela of radical prostatectomy. The etiology involves injury to the autonomic cavernous nerves, which arise from the major pelvic ganglion (MPG), and subsequent neuroinflammation, which leads to recruitment of macrophages to the injury site. Currently, two macrophage phenotypes are known: neurotoxic M1 macrophages and neuroprotective M2 macrophages. AIM: To examine whether bilateral cavernous nerve injury (BCNI) in a rat model of erectile dysfunction would increase recruitment of neurotoxic M1 macrophages to the MPG...
February 2017: Journal of Sexual Medicine
https://www.readbyqxmd.com/read/28153659/enoxaparin-for-the-prevention-of-preeclampsia-and%C3%A2-intrauterine-growth-restriction-in-women-with%C3%A2-a%C3%A2-history-%C3%A2-a%C3%A2-randomized-trial
#19
Katie M Groom, Lesley M McCowan, Laura K Mackay, Arier C Lee, Joanne M Said, Stefan C Kane, Susan P Walker, Thijs E van Mens, Natalie J Hannan, Stephen Tong, Larry W Chamley, Peter R Stone, Claire McLintock
BACKGROUND: Preeclampsia and small-for-gestational-age pregnancy are major causes of maternal and perinatal morbidity and mortality. Women with a previous pregnancy affected by these conditions are at an increased risk of recurrence in a future pregnancy. Past trials evaluating the effect of low-molecular-weight heparin for the prevention of recurrence of preeclampsia and small-for-gestational-age pregnancy have shown conflicting results with high levels of heterogeneity displayed when trials were compared...
March 2017: American Journal of Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28121616/investigation-of-antinociceptive-activity-of-methanolic-extract-of-persicaria-orientalis-leaves-in-rodents
#20
Prawej Ansari, Md Josim Uddin, Shafia Akther, Shofiul Azam, Md Kayes Mahmud, Sohel Bin Azad, Ahsan Ullah, J M A Hannan
BACKGROUND: This study aims to evaluate the scientific basis of traditional application of Persicaria orientalis for reducing pain and inflammation. METHODS: An in vitro method was performed to investigate the presence of the anti-inflammatory activity of methanolic crude extract of P. orientalis. In addition, an in vivo study was conducted in which the hot-plate and tail immersion methods were applied to explore the acute effect of P. orientalis on analgesia. The potency to inhibit chronic inflammation in mice was justified by the carrageenan-induced paw edema and formalin-induced edema methods...
March 1, 2017: Journal of Basic and Clinical Physiology and Pharmacology
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