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The pleiotropic deubiquitinase Ubp3 confers aneuploidy tolerance. - Genes & development
Aneuploidy-or an unbalanced karyotype in which whole chromosomes are gained or lost-causes reduced fitness at both the cellular and organismal levels but is also a hallmark of human cancers. Aneuploidy causes a variety of cellular stresses, including genomic instability, proteotoxic and oxidative stresses, and impaired protein trafficking. The deubiquitinase Ubp3, which was identified by a genome-wide screen for gene deletions that impair the fitness of aneuploid yeast, is a key regulator of aneuploid cell homeostasis. We show that deletion of UBP3 exacerbates both karyotype-specific phenotypes and global stresses of aneuploid cells, including oxidative and proteotoxic stress. Indeed, Ubp3 is essential for proper proteasome function in euploid cells, and deletion of this deubiquitinase leads to further proteasome-mediated proteotoxicity in aneuploid yeast. Notably, the importance of UBP3 in aneuploid cells is conserved. Depletion of the human homolog of UBP3, USP10, is detrimental to the fitness of human cells upon chromosome missegregation, and this fitness defect is accompanied by autophagy inhibition. We thus used a genome-wide screen in yeast to identify a guardian of aneuploid cell fitness conserved across species. We propose that interfering with Ubp3/USP10 function could be a productive avenue in the development of novel cancer therapeutics.Â© 2016 Dodgson et al.; Published by Cold Spring Harbor Laboratory Press.
12th WINFOCUS world congress on ultrasound in emergency and critical care. - Critical ultrasound journal
A1 Point-of-care ultrasound examination of cervical spine in emergency departmentYahya Acar, Onur Tezel, Necati SalmanA2 A new technique in verifying the placement of a nasogastric tube: obtaining the longitudinal view of nasogastric tube in addition to transverse view with ultrasoundYahya Acar, Necati Salman, Onur Tezel, Erdem CevikA3 Pseudoaneurysm of the femoral artery after cannulation of a central venous line. Should we always use ultrasound in these procedures?Margarita Algaba-Montes, Alberto Oviedo-GarcÃa, Mayra Patricio-BordomÃ¡sA4 Ultrasound-guided supraclavicular subclavian vein catheterization. A novel approach in emergency departmentMargarita Algaba-Montes, Alberto Oviedo-GarcÃa, Mayra Patricio-BordomÃ¡sA5 Clinical ultrasound in a septic and jaundice patient in the emergency departmentMargarita Algaba-Montes, Alberto Oviedo-GarcÃa, Mayra Patricio-BordomÃ¡sA6 Characterization of the eyes in preoperative cataract Saudi patients by using medical diagnostic ultrasoundMustafa Z. Mahmoud, Abdelmoneim SuliemanA7 High-frequency ultrasound in determining the causes of acute shoulder joint painMustafa Z. MahmoudA8 Teaching WINFOCUS Ultrasound Life Support Basic Level 1 for Providers in resource-limited countriesAbbas Ali, Alrayah Mustafa, Ihab Abdelrahman, Mustafa Bahar, Osama Ali, H. Lester Kirchner, Gregor ProsenA9 Changes of arterial stiffness and endothelial function during uncomplicated pregnancyAjda Anzic, Paul LeesonA10 Cardiovascular haemodynamic properties before, during and after pregnancyAjda Anzic, Paul LeesonA11 An old man with generalized weaknessMaryam Bahreini, Fatemeh RasooliA12 Ultrasonography for non-specific presentations of abdominal painMaryam Bahreini, Houman HosseinnejadA13 Introduction of a new imaging guideline for suspected renal colic in the emergency department: effect on CT Urogram utilisationGabriel Blecher, Robert Meek, Diana Egerton-WarburtonA14 Transabdominal ultrasound screening for pancreatic cancer in Croatian military veterans: a retrospective analysis from the first Croatian veteran's hospitalEdina Ä†atiÄ‡ Ä†uti, Stanko Belina, Tihomir VanÄina, Idriz KovaÄeviÄ‡A15 The challenge of AAA: unusual case of obstructive jaundiceEdina Ä†atiÄ‡ Ä†uti, Nadan RustemoviÄ‡A16 Educational effectiveness of easy-made new simulator model for ultrasound-guided procedures in pediatric patients: vascular access and foreign body managementIkwan Chang, Jin Hee Lee, Young Ho Kwak, Do Kyun KimA17 Detection of uterine rupture by point-of-care ultrasound at emergency department: a case reportChi-Yung Cheng, Hsiu-Yung Pan, Chia-Te KungA18 Abdominal probe in the hands of interns as a relevant diagnostic tool in revealing the cause of heart failureEla Ä†urÄiÄ‡, Ena PritiÅ¡anac, Ivo Planinc, Marijana GrgiÄ‡ MediÄ‡, Radovan RadoniÄ‡A19 Needs assessment of the potential utility of point-of-care ultrasound within the Zanzibar health systemAbiola Fasina, Anthony J. Dean, Nova L. Panebianco, Patricia S. HenwoodA20 Ultrasonographic diagnosis of tracheal compressionOliviero Fochi, Moreno Favarato, Ezio BonanomiA21 The role of ultrasound in the detection of lung infiltrates in critically ill patients: a pilot studyMarijana GrgiÄ‡ MediÄ‡, Ivan TomiÄ‡, Radovan RadoniÄ‡A22 The SAFER Lasso; a novel approach using point-of-care ultrasound to evaluate patients with abdominal complaints in the emergency departmentYoungrock Ha, Hongchuen TohA23 Awareness and use of clinician-performed ultrasound among clinical clerkship facultyElizabeth Harmon, Wilma Chan, Cameron Baston, Gail Morrison, Frances Shofer, Nova Panebianco, Anthony J. DeanA24 Clinical outcomes in the use of lung ultrasound for the diagnosis of pediatric pneumoniasAngela Hua, Sharon Kim, James TsungA25 Effectiveness of ultrasound in hypotensive patientsIsa Gunaydin, Zeynep Kekec, Mehmet Oguzhan AyA26 Moderate-to-severe left ventricular ejection fraction related to short-term mortality of patients with post-cardiac arrest syndrome after out-of-hospital cardiac arrestJinjoo Kim, Jinhyun Kim, Gyoosung Choi, Dowon ShimA27 Usefulness of abdominal ultrasound for acute pyelonephritis diagnosis after kidney transplantationJi-Han LeeA28 Lung ultrasound for assessing fluid tolerance in severe preeclampsiaJana Ambrozic, Katja Prokselj, Miha LucovnikA29 Optic nerve sheath ultrasound in severe preeclampsiaGabrijela Brzan Simenc, Jana Ambrozic, Miha LucovnikA30 Focused echocardiography monitoring in the postoperative period for non-cardiac patientsAsta MaÄiulienÄ—, Almantas Maleckas, Algimantas KriÅ¡Äiukaitis, Vytautas MaÄiulis, Andrius MacasA31 POCUS-guided paediatric upper limb fracture reduction: algorithm, tricks, and tipsSharad MohiteA32 Point-of-care lung ultrasound: a good diagnostic tool for pneumonia in a septic patientZoltan Narancsik, Hugon MoÅ¾inaA33 A case of undergraduate POCUS (r)evolutionSara NikoliÄ‡, Jan Hansel, Rok PetrovÄiÄ, Una MrÅ¡iÄ‡, Gregor ProsenA34 The Graz Summer School for ultrasound: from first contact to bedside application: three-and-a-half-day undergraduate ultrasound training: rÃ©sumÃ© after two years of continuous developmentSimon Orlob, Markus Lerchbaumer, Niklas SchÃ¶negger, Reinhard KaufmannA35 Usefulness of point-of-care ultrasound in the emergency room in a patient with acute abdominal painAlberto Oviedo-GarcÃa, Margarita Algaba-Montes, Mayra Patricio-BordomÃ¡sA36 Use of bedside ultrasound in a critically ill patient. A case reportAlberto Oviedo-GarcÃa, Margarita Algaba-Montes, Mayra Patricio-BordomÃ¡sA37 Diagnostic yield of clinical echocardiography for the emergency physicianAlberto Oviedo-GarcÃa, Margarita Algaba-Montes, Mayra Patricio-BordomÃ¡sA38 Focused cardiac ultrasound in early diagnosis of type A aortic dissection with atypical presentationChun-I Pan, Hsiu-Yung Pan, Chien-Hung WuA39 Detection of imperforated hymen by point-of-care ultrasoundHsiu-yung Pan, Chia-Te KungA40 Developing a point-of-care ultrasound curriculum for pediatric nurse practitioners practicing in the pediatric emergency departmentSarah Pasquale, Stephanie J. Doniger, Sharon Yellin, Gerardo ChiricoloA41 Use of transthoracic echocardiography in emergency setting: patient with mitral valve abscessMaja Potisek, Borut DrnovÅ¡ek, BoÅ¡tjan LeskovarA42 A young man with syncopeFatemeh Rasooli, Maryam BahreiniA43 Work-related repetitive use injuries in ultrasound fellowsKristine Robinson, Clara Kraft, Benjamin Moser, Stephen Davis, Shelley Layman, Yusef Sayeed, Joseph MinardiA44 Lung ultrasonography in the evaluation of pneumonia in childrenIrmina Sefic Pasic, Amra Dzananovic, Anes Pasic, Sandra Vegar ZubovicA45 Central venous catheter placement with the ultrasound aid: two years' experience of the Interventional unit, Division of Intensive Care Medicine, KBC ZagrebAna Godan Hauptman, Marijana Grgic Medic, Ivan Tomic, Ana Vujaklija Brajkovic, Jaksa Babel, Marina Peklic, Radovan RadonicA46 Duplicitas casui: two patients admitted due to acute liver failureVedran Radonic, Ivan Tomic, Luka Bielen, Marijana Grgic MedicA47 A pilot survey on an understanding of Bedside Point-of-Care Ultrasound (POCUS) among medical doctors in internal medicine: exposure, perceptions, interest, and barriers to trainingPeh Wee MingA48 Unusual case of defecation syncopeNur hafiza Yezid, Fatahul Laham MohammedA49 A case report of massive pulmonary embolism; a multidisciplinary approachZainal Abidin Huda, Wan Nasarudin Wan Ismail, W.Yus Haniff W.Isa, Hashairi Fauzi, Praveena Seeva, Mohd Zulfakar Mazlan.
Wide-field optical mapping of neural activity and brain haemodynamics: considerations and novel approaches. - Philosophical transactions of the Royal Society of London. Series B, Biological sciences
Although modern techniques such as two-photon microscopy can now provide cellular-level three-dimensional imaging of the intact living brain, the speed and fields of view of these techniques remain limited. Conversely, two-dimensional wide-field optical mapping (WFOM), a simpler technique that uses a camera to observe large areas of the exposed cortex under visible light, can detect changes in both neural activity and haemodynamics at very high speeds. Although WFOM may not provide single-neuron or capillary-level resolution, it is an attractive and accessible approach to imaging large areas of the brain in awake, behaving mammals at speeds fast enough to observe widespread neural firing events, as well as their dynamic coupling to haemodynamics. Although such wide-field optical imaging techniques have a long history, the advent of genetically encoded fluorophores that can report neural activity with high sensitivity, as well as modern technologies such as light emitting diodes and sensitive and high-speed digital cameras have driven renewed interest in WFOM. To facilitate the wider adoption and standardization of WFOM approaches for neuroscience and neurovascular coupling research, we provide here an overview of the basic principles of WFOM, considerations for implementation of wide-field fluorescence imaging of neural activity, spectroscopic analysis and interpretation of results.This article is part of the themed issue 'Interpreting BOLD: a dialogue between cognitive and cellular neuroscience'.Â© 2016 The Authors.
Rapid Postnatal Expansion of Neural Networks Occurs in an Environment of Altered Neurovascular and Neurometabolic Coupling. - The Journal of neuroscience : the official journal of the Society for Neuroscience
In the adult brain, increases in neural activity lead to increases in local blood flow. However, many prior measurements of functional hemodynamics in the neonatal brain, including functional magnetic resonance imaging (fMRI) in human infants, have noted altered and even inverted hemodynamic responses to stimuli. Here, we demonstrate that localized neural activity in early postnatal mice does not evoke blood flow increases as in the adult brain, and elucidate the neural and metabolic correlates of these altered functional hemodynamics as a function of developmental age. Using wide-field GCaMP imaging, the development of neural responses to somatosensory stimulus is visualized over the entire bilaterally exposed cortex. Neural responses are observed to progress from tightly localized, unilateral maps to bilateral responses as interhemispheric connectivity becomes established. Simultaneous hemodynamic imaging confirms that spatiotemporally coupled functional hyperemia is not present during these early stages of postnatal brain development, and develops gradually as cortical connectivity is established. Exploring the consequences of this lack of functional hyperemia, measurements of oxidative metabolism via flavoprotein fluorescence suggest that neural activity depletes local oxygen to below baseline levels at early developmental stages. Analysis of hemoglobin oxygenation dynamics at the same age confirms oxygen depletion for both stimulus-evoked and resting-state neural activity. This state of unmet metabolic demand during neural network development poses new questions about the mechanisms of neurovascular development and its role in both normal and abnormal brain development. These results also provide important insights for the interpretation of fMRI studies of the developing brain.This work demonstrates that the postnatal development of neuronal connectivity is accompanied by development of the mechanisms that regulate local blood flow in response to neural activity. Novel in vivo imaging reveals that, in the developing mouse brain, strong and localized GCaMP neural responses to stimulus fail to evoke local blood flow increases, leading to a state in which oxygen levels become locally depleted. These results demonstrate that the development of cortical connectivity occurs in an environment of altered energy availability that itself may play a role in shaping normal brain development. These findings have important implications for understanding the pathophysiology of abnormal developmental trajectories, and for the interpretation of functional magnetic resonance imaging data acquired in the developing brain.Copyright Â© 2016 the authors 0270-6474/16/366704-14$15.00/0.
Using Bundled Interventions to Reduce Surgical Site Infection After Major Gynecologic Cancer Surgery. - Obstetrics and gynecology
To investigate whether implementing a bundle, defined as a set of evidence-based practices performed collectively, can reduce 30-day surgical site infections.Baseline surgical site infection rates were determined retrospectively for cases of open uterine cancer, ovarian cancer without bowel resection, and ovarian cancer with bowel resection between January 1, 2010, and December 31, 2012, at an academic center. A perioperative bundle was prospectively implemented during the intervention period (August 1, 2013, to September 30, 2014). Prior established elements were: patient education, 4% chlorhexidine gluconate shower before surgery, antibiotic administration, 2% chlorhexidine gluconate and 70% isopropyl alcohol coverage of incisional area, and cefazolin redosing 3-4 hours after incision. New elements initiated were: sterile closing tray and staff glove change for fascia and skin closure, dressing removal at 24-48 hours, dismissal with 4% chlorhexidine gluconate, and follow-up nursing phone call. Surgical site infection rates were examined using control charts, compared between periods using Ï‡ or Fisher exact test, and validated against the American College of Surgeons National Surgical Quality Improvement Program decile ranking.The overall 30-day surgical site infection rate was 38 of 635 (6.0%) among all cases in the preintervention period, with 11 superficial (1.7%), two deep (0.3%), and 25 organ or space infections (3.9%). In the intervention period, the overall rate was 2 of 190 (1.1%), with two organ or space infections (1.1%). Overall, the relative risk reduction in surgical site infection was 82.4% (P=.01). The surgical site infection relative risk reduction was 77.6% among ovarian cancer with bowel resection, 79.3% among ovarian cancer without bowel resection, and 100% among uterine cancer. The American College of Surgeons National Surgical Quality Improvement Program decile ranking improved from the 10th decile to first decile; risk-adjusted odds ratio for surgical site infection decreased from 1.6 (95% confidence interval 1.0-2.6) to 0.6 (0.3-1.1).Implementation of an evidence-based surgical site infection reduction bundle was associated with substantial reductions in surgical site infection in high-risk cancer procedures.
Hepatic Dysfunction in Patients Receiving Intravenous Amiodarone. - Southern medical journal
Amiodarone is a commonly used antiarrhythmic drug. Hepatotoxicity following chronic oral administration occurs in 1% to 3% of patients. Hepatotoxicity following intravenous (IV) administration is infrequent but may be associated with dramatic increases in serum transaminases. We describe the incidence of liver toxicity among patients receiving IV amiodarone during a 5-year period.This was a single-center retrospective review of patients receiving IV amiodarone for any cause. The outcome measures were development of elevated serum transaminases and the relation of transaminitis to all-cause 30-day mortality.A total of 1510 patients received amiodarone intravenously between 2005 and 2011; 77 (5%) developed elevated liver enzymes. Enzyme elevation was divided into mild (100-300 IU/L), moderate (300-1000 IU/L), and severe (>1000 IU/L). The median alanine aminotransferase was 189 (37-10,006) IU/L and aspartate aminotransferase was 253 (84-12,005) IU/L. The 30-day mortality among those with transaminitis was 22%; however, no patient died of amiodarone-related liver disease.Amiodarone can cause severe elevation in liver enzymes. The incidence of severe transaminitis is low; deaths following IV amiodarone are rarely caused by drug-induced liver failure.
Chromosome-Specific and Global Effects of Aneuploidy in Saccharomyces cerevisiae. - Genetics
Aneuploidy, an unbalanced karyotype in which one or more chromosomes are present in excess or reduced copy number, causes an array of known phenotypes including proteotoxicity, genomic instability, and slowed proliferation. However, the molecular consequences of aneuploidy are poorly understood and an unbiased investigation into aneuploid cell biology is lacking. We performed high-throughput screens for genes the deletion of which has a synthetic fitness cost in aneuploidy Saccharomyces cerevisiae cells containing single extra chromosomes. This analysis identified genes that, when deleted, decrease the fitness of specific disomic strains as well as those that impair the proliferation of a broad range of aneuploidies. In one case, a chromosome-specific synthetic growth defect could be explained fully by the specific duplication of a single gene on the aneuploid chromosome, highlighting the ability of individual dosage imbalances to cause chromosome-specific phenotypes in aneuploid cells. Deletion of other genes, particularly those involved in protein transport, however, confers synthetic sickness on a broad array of aneuploid strains. Indeed, aneuploid cells, regardless of karyotype, exhibit protein secretion and cell-wall integrity defects. Thus, we were able to use this screen to identify novel cellular consequences of aneuploidy, dependent on both specific chromosome imbalances and caused by many different aneuploid karyotypes. Interestingly, the vast majority of cancer cells are highly aneuploid, so this approach could be of further use in identifying both karyotype-specific and nonspecific stresses exhibited by cancer cells as potential targets for the development of novel cancer therapeutics.Copyright Â© 2016 by the Genetics Society of America.
Electrical stimulation for gastroesophageal reflux disease: current state of the art. - Clinical and experimental gastroenterology
Patients with gastroesophageal reflux disease (GERD) who are not satisfied with acid suppression therapy can benefit primarily from fundoplication, a surgical intervention. Fundoplication has been the standard surgical procedure for GERD. It is effective but is associated with adverse effects, resulting in a declining number of interventions, creating a need for alternative interventions that are effective, yet have a better adverse effect profile. One such alternative involves the application of electrical stimulation to the lower esophageal sphincter. A number of animal studies showed that such stimulation can increase resting lower esophageal sphincter pressure. An acute human study confirmed this effect, and was followed by two open-label studies, with a follow-up of up to 3 years. Results thus far show that the therapy is associated with a significant improvement in symptoms, a significant reduction in esophageal acid exposure, and a very good safety profile. This review will describe the evolution of electrical stimulation therapy for GERD, as well as the safety and efficacy of this intervention.
Ventricular fibrillation after elective surgery in an adolescent with long QT syndrome. - BMJ case reports
Congenital long QT syndrome (LQTS) is a potentially lethal but highly treatable channelopathy. Along with multiple risk reduction measures, a recommendation for left sympathetic cardiac denervation therapy and/or implantable cardioverter defibrillator is made for higher risk patients. Despite its relatively common incidence in paediatric patients, there are no formal recommendations regarding perioperative management and discharge criteria for LQTS patients undergoing ambulatory surgery. This report describes a 17-year-old girl, diagnosed with congenital LQTS at 9 years of age, who had an episode of ventricular fibrillation the day after elective ear, nose and throat surgery. Despite several risk factors, she had a same-day dismissal, was not adequately monitored postoperatively and her cardiologists were not notified of her procedure. For the high-risk LQTS patient, we recommend monitoring of perioperative electrolytes and rhythm, postoperative ECG, adequate Î²-blockade therapy, avoidance of particular pharmacological agents, consideration of overnight observation and communication with the patient's cardiologist prior to procedure, and at discharge.2015 BMJ Publishing Group Ltd.
An RNAi-Based Candidate Screen for Modifiers of the CHD1 Chromatin Remodeler and Assembly Factor in Drosophila melanogaster. - G3 (Bethesda, Md.)
The conserved chromatin remodeling and assembly factor CHD1 (chromodomains, helicase, DNA-binding domain) is present at active genes where it participates in histone turnover and recycling during transcription. In order to gain a more complete understanding of the mechanism of action of CHD1 during development, we created a novel genetic assay in Drosophila melanogaster to evaluate potential functional interactions between CHD1 and other chromatin factors. We found that overexpression of CHD1 results in defects in wing development and utilized this fully penetrant and reliable phenotype to conduct a small-scale RNAi-based candidate screen to identify genes that functionally interact with chd1 in vivo. Our results indicate that CHD1 may act in opposition to other remodeling factors, including INO80, and that the recruitment of CHD1 to active genes by RTF1 is conserved in flies.Copyright Â© 2016 Kim et al.
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