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https://www.readbyqxmd.com/read/28820965/systematic-identification-of-mcu-modulators-by-orthogonal-interspecies-chemical-screening
#1
Daniela M Arduino, Jennifer Wettmarshausen, Horia Vais, Paloma Navas-Navarro, Yiming Cheng, Anja Leimpek, Zhongming Ma, Alba Delrio-Lorenzo, Andrea Giordano, Cecilia Garcia-Perez, Guillaume Médard, Bernhard Kuster, Javier García-Sancho, Dejana Mokranjac, J Kevin Foskett, M Teresa Alonso, Fabiana Perocchi
The mitochondrial calcium uniporter complex is essential for calcium (Ca(2+)) uptake into mitochondria of all mammalian tissues, where it regulates bioenergetics, cell death, and Ca(2+) signal transduction. Despite its involvement in several human diseases, we currently lack pharmacological agents for targeting uniporter activity. Here we introduce a high-throughput assay that selects for human MCU-specific small-molecule modulators in primary drug screens. Using isolated yeast mitochondria, reconstituted with human MCU, its essential regulator EMRE, and aequorin, and exploiting a D-lactate- and mannitol/sucrose-based bioenergetic shunt that greatly minimizes false-positive hits, we identify mitoxantrone out of more than 600 clinically approved drugs as a direct selective inhibitor of human MCU...
August 17, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28820702/predictive-model-for-permanent-shunting-in-cryptococcal-meningitis
#2
Woralux Phusoongnern, Siriluck Anunnatsiri, Kittisak Sawanyawisuth, Amnat Kitkhuandee
Cryptococcal meningitis may have long-term morbidity and requires a permanent cerebrospinal fluid shunt. This study aimed to evaluate the risk factors and create a predictive model for permanent shunt treatment in cryptococcal meningitis patients. This was a retrospective analytical study conducted at Khon Kaen University. The study period was from January 2005 to December 2015. We enrolled all adult patients diagnosed with cryptococcal meningitis. Risk factors predictive for permanent shunting treatment were analyzed by multivariate logistic regression analysis...
August 14, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28817574/diffusion-tensor-imaging-profiles-reveal-specific-neural-tract-distortion-in-normal-pressure-hydrocephalus
#3
Nicole C Keong, Alonso Pena, Stephen J Price, Marek Czosnyka, Zofia Czosnyka, Elise E DeVito, Charlotte R Housden, Barbara J Sahakian, John D Pickard
BACKGROUND: The pathogenesis of normal pressure hydrocephalus (NPH) remains unclear which limits both early diagnosis and prognostication. The responsiveness to intervention of differing, complex and concurrent injury patterns on imaging have not been well-characterized. We used diffusion tensor imaging (DTI) to explore the topography and reversibility of white matter injury in NPH pre- and early after shunting. METHODS: Twenty-five participants (sixteen NPH patients and nine healthy controls) underwent DTI, pre-operatively and at two weeks post-intervention in patients...
2017: PloS One
https://www.readbyqxmd.com/read/28816631/platypnea-orthodeoxia-syndrome-an-unusual-presentation-of-a-complex-disease
#4
Tess Van Meerhaeghe, Steven Droogmans, Shane Hanon, Jeroen Sonck
BACKGROUND: Platypnea-orthodeoxia syndrome (POS) is an uncommon disorder characterized by dyspnea (=platypnea) and desaturation (=orthodeoxia) in upright position and improvement of symptoms and blood oxygenation in supine position. Clinical presentation is heterogeneous and often confuses the clinician. OBJECTIVES: The present case report illustrates a complicated presentation of the underlying syndrome. METHODS: Description of a POS case in a 73-year-old female with thorough workup and tailored treatment...
August 17, 2017: Acta Clinica Belgica
https://www.readbyqxmd.com/read/28815088/use-of-anti-vegf-agents-in-glaucoma-surgery
#5
REVIEW
Mark Slabaugh, Sarwat Salim
A number of antivascular endothelial growth factor agents are currently available to treat various ocular conditions. These agents have similar, but distinct, biologic qualities and have been explored in the management of neovascular glaucoma and in glaucoma surgery. Several different delivery methods are described, and because these medications are routinely given as intraocular injections, some benefits over traditional antifibrotic medications when used in glaucoma surgery are noted. These agents effectively induce regression of anterior segment neovascularization and facilitate initial surgical management of neovascular glaucoma, but the long-term outcome of this condition remains dependent on definitive management of the underlying process...
2017: Journal of Ophthalmology
https://www.readbyqxmd.com/read/28814705/-spontaneous-subcapsular-renal-hemorrhage-of-papillary-renal-cell-carcinoma
#6
Masatsugu Miyashita, Tsuyoshi Iwata, Hiroyuki Nakanishi, Jintetsu Soh
A 75-year-old man with a history of chronic kidney disease (CKD) visited our emergency room after the sudden onset of severe right lower abdominal pain and nausea. Computed tomography (CT) showed right perirenal hematoma and renal tumor, which was diagnosed as a spontaneous rupture of the right renal tumor. It was difficult to correctly diagnose the tumor as benign or malignant with magnetic resonance imaging (MRI). Because of CKD, a shunt was implanted, and dynamic enhanced CT was performed. Dynamic enhanced CT showed a slightly enhanced area of the tumor, and it was diagnosed as renal cell carcinoma (RCC)...
July 2017: Hinyokika Kiyo. Acta Urologica Japonica
https://www.readbyqxmd.com/read/28814595/bleeding-ectopic-duodenal-varix-use-of-a-new-microvascular-plug-mvp-device-along-with-transjugular-intrahepatic-portosystemic-shunt-tipss
#7
Richa Bhardwaj, Gaurav Bhardwaj, Erik Bee, Raffi Karagozian
Ectopic varices (ECV) occur along the gastrointestinal (GI) tract outside the common variceal sites and represent 2%-5% of all GI variceal bleeds with mortality rates up to 40%. Management is challenging because of inaccessibility and increased risk of rebleeding. We report what is to our knowledge the first clinical use of a new microvascular plug (MVP) with transjugular intrahepatic portosystemic shunt (TIPSS) for a bleeding duodenal varix (DV). A 68-year-old man presented with melena. Endoscopy demonstrated a grade II varix in the second part of the duodenum with red wale sign...
August 16, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28814489/right-ventricular-outflow-tract-stent-versus-bt-shunt-palliation-in-tetralogy-of-fallot
#8
Daniel Quandt, Bharat Ramchandani, Gemma Penford, John Stickley, Vinay Bhole, Chetan Mehta, Timothy Jones, David James Barron, Oliver Stumper
OBJECTIVE: This study sets out to compare morbidity, mortality and reintervention rates after stenting of the right ventricular outflow tract (RVOT) versus modified Blalock-Taussig shunt (mBTS) for palliation in patients with tetralogy of Fallot (ToF)-type lesions. METHODS: Retrospective case review study evaluating 101 patients (64 males) with ToF lesions who underwent palliation with either mBTS (n=41) or RVOT stent (n=60) to augment pulmonary blood flow over a 10-year period...
August 16, 2017: Heart: Official Journal of the British Cardiac Society
https://www.readbyqxmd.com/read/28814334/abernethy-malformation-associated-with-caroli-s-syndrome-in-a-patient-with-a-pkhd1-mutation-a-case-report
#9
Xiao-Xiao Mi, Xiao-Guang Li, Zi-Rong Wang, Ling Lin, Chun-Hai Xu, Jun-Ping Shi
BACKGROUND: Abernethy malformation is a rare congenital anomaly characterised by the partial or complete absence of the portal vein and the subsequent development of an extrahepatic portosystemic shunt. Caroli's disease is a rare congenital condition characterised by non-obstructive saccular intrahepatic bile duct dilation. Caroli's disease combined with congenital hepatic fibrosis and/or renal cystic disease is referred to - Caroli's syndrome. The combination of Abernethy malformation and Caroli's syndrome has not been reported previously...
August 16, 2017: Diagnostic Pathology
https://www.readbyqxmd.com/read/28813763/simultaneous-onset-of-deep-vein-thrombosis-pulmonary-embolism-cerebral-infarction-and-myocardial-infarction-in-a-patient-with-patent-foramen-ovale
#10
Jimmy Yee, Vishesh Kumar, Alex Pham, Kashif Shaikh, Muhammad Omar, Adam Stys, Marian Petrasko
Paradoxical embolism is a known complication with intra-cardiac shunts. It should be considered in the differential as the pathophysiologic mechanism of simultaneous thromboembolism in the venous and systemic vasculature. We present a case of simultaneous deep venous thrombosis, pulmonary embolism and myocardial infarction in the presence of a confirmed patent foramen ovale on echocardiography. Thrombolytic therapy was administered. Subsequent concerns of intracranial hemorrhage on imaging of the brain complicated the management and added to the challenge of co-managing the clot burden in our patient...
June 2017: South Dakota Medicine: the Journal of the South Dakota State Medical Association
https://www.readbyqxmd.com/read/28812671/sulfate-radicals-enable-a-non-enzymatic-krebs-cycle-precursor
#11
Markus A Keller, Domen Kampjut, Stuart A Harrison, Markus Ralser
The evolutionary origins of the Krebs cycle (tricarboxylic acid cycle) are not currently clear. Despite the existence of a simple non-enzymatic Krebs cycle catalyst being dismissed only a few years ago as 'an appeal to magic', citrate and other intermediates have since been discovered on a carbonaceous meteorite and do interconvert non-enzymatically. To identify a metabolism-like non-enzymatic Krebs cycle catalyst, we used combinatorial, quantitative high-throughput metabolomics to systematically screen iron and sulfate compounds in a reaction mixture that orients on the typical components of Archaean sediment...
March 13, 2017: Nature ecology & evolution
https://www.readbyqxmd.com/read/28811719/refractory-hepatic-encephalopathy-in-a-patient-with-hypothyroidism-another-element-in-ammonia-metabolism
#12
Fernando Díaz-Fontenla, Marta Castillo-Pradillo, Arantxa Díaz-Gómez, Luis Ibañez-Samaniego, Pilar Gancedo, Juan Adan Guzmán-de-Villoria, Pilar Fernández-García, Rafael Bañares-Cañizares, Rita García-Martínez
Hepatic encephalopathy (HE) remains a diagnosis of exclusion due to the lack of specific signs and symptoms. Refractory HE is an uncommon but serious condition that requires the search of hidden precipitating events (i.e., portosystemic shunt) and alternative diagnosis. Hypothyroidism shares clinical manifestations with HE and is usually considered within the differential diagnosis of HE. Here, we describe a patient with refractory HE who presented a large portosystemic shunt and post-ablative hypothyroidism...
July 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28811348/a-critical-role-of-glutamine-and-asparagine-%C3%AE-nitrogen-in-nucleotide-biosynthesis-in-cancer-cells-hijacked-by-an-oncogenic-virus
#13
Ying Zhu, Tingting Li, Suzane Ramos da Silva, Jae-Jin Lee, Chun Lu, Hyungjin Eoh, Jae U Jung, Shou-Jiang Gao
While glutamine is a nonessential amino acid that can be synthesized from glucose, some cancer cells primarily depend on glutamine for their growth, proliferation, and survival. Numerous types of cancer also depend on asparagine for cell proliferation. The underlying mechanisms of the glutamine and asparagine requirement in cancer cells in different contexts remain unclear. In this study, we show that the oncogenic virus Kaposi's sarcoma-associated herpesvirus (KSHV) accelerates the glutamine metabolism of glucose-independent proliferation of cancer cells by upregulating the expression of numerous critical enzymes, including glutaminase 2 (GLS2), glutamate dehydrogenase 1 (GLUD1), and glutamic-oxaloacetic transaminase 2 (GOT2), to support cell proliferation...
August 15, 2017: MBio
https://www.readbyqxmd.com/read/28811093/risk-factors-for-infective-endocarditis-in-children-with-congenital-heart-diseases-a-nationwide-population-based-case-control-study
#14
Li-Chuan Sun, Chih-Cheng Lai, Cheng-Yi Wang, Ya-Hui Wang, Jen-Yu Wang, Yo-Ling Hsu, Yin-Lan Hu, En-Ting Wu, Ming-Tai Lin, Leticia B Sy, Likwang Chen
BACKGROUND: Infective endocarditis (IE) is uncommon in childhood. Its associated epidemiological characteristics in patients with congenital heart disease (CHD) remain unclear. METHODS: The study population included children born in Taiwan during the years 1997 to 2005 who were diagnosed as having CHD before 3years of age. All children were followed up until the end year of 2010, the diagnosis of infective endocarditis, or death. The demographic characteristics of patients with and without IE, the invasive procedures performed during 6months before the index date, the prophylactic antibiotics related to dental procedures, and in-hospital mortality were collected...
August 12, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28810163/decoding-the-architecture-and-origins-of-mechanisms-for-developmental-polyphenism
#15
REVIEW
Joana Projecto-Garcia, Joseph F Biddle, Erik J Ragsdale
Developmental polyphenism affords a single genotype multiple solutions to match an organism to its environment. Because polyphenism is the extreme example of how development deviates from a linear genetic blueprint, it demands a genetic explanation for how environmental cues shunt development to hypothetically alternative modules. We highlight several recent advances that have begun to illuminate genetic mechanisms for polyphenism and how this recurring developmental novelty may arise. An emerging genetic knowledge of polyphenism is providing precise targets for testing hypotheses of how switch mechanisms are built-out of olfactory, nutrient-sensing, hormone-reception, and developmental and genetic buffering systems-to accommodate plasticity...
August 12, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/28810087/multiple-pulmonary-arteriovenous-malformations-an-unusual-cause-of-shortness-of-breath-and-recurrent-strokes
#16
Kalyan C Potu, Shenjing Li, Shawn C Kelly, Julia A Prescott-Focht, Scott Pham
OBJECTIVE: To discuss an uncommon case of a patient with multiple pulmonary arteriovenous malformations (PAVMs) presenting with dyspnea on exertion and recurrent strokes. BACKGROUND: A 79-year-old woman with recent onset recurrent cerebrovascular accidents (CVAs) was referred to cardiology for evaluation of dyspnea on exertion. Clinical examination was unrevealing. METHODS: A transthoracic echocardiogram (TTE) with agitated saline was suggestive of an extra-cardiac shunt...
February 2017: South Dakota Medicine: the Journal of the South Dakota State Medical Association
https://www.readbyqxmd.com/read/28808803/a-prototype-educational-model-for-hepatobiliary-interventions-unveiling-the-role-of-graphic-designers-in-medical-3d-printing
#17
Ramin Javan, Merissa N Zeman
In the context of medical three-dimensional (3D) printing, in addition to 3D reconstruction from cross-sectional imaging, graphic design plays a role in developing and/or enhancing 3D-printed models. A custom prototype modular 3D model of the liver was graphically designed depicting segmental anatomy of the parenchyma containing color-coded hepatic vasculature and biliary tree. Subsequently, 3D printing was performed using transparent resin for the surface of the liver and polyamide material to develop hollow internal structures that allow for passage of catheters and wires...
August 14, 2017: Journal of Digital Imaging: the Official Journal of the Society for Computer Applications in Radiology
https://www.readbyqxmd.com/read/28808255/critical-role-for-arginase-2-in-obesity-associated-pancreatic-cancer
#18
Tamara Zaytouni, Pei-Yun Tsai, Daniel S Hitchcock, Cory D DuBois, Elizaveta Freinkman, Lin Lin, Vicente Morales-Oyarvide, Patrick J Lenehan, Brian M Wolpin, Mari Mino-Kenudson, Eduardo M Torres, Nicholas Stylopoulos, Clary B Clish, Nada Y Kalaany
Obesity is an established risk factor for pancreatic ductal adenocarcinoma (PDA). Despite recent identification of metabolic alterations in this lethal malignancy, the metabolic dependencies of obesity-associated PDA remain unknown. Here we show that obesity-driven PDA exhibits accelerated growth and a striking transcriptional enrichment for pathways regulating nitrogen metabolism. We find that the mitochondrial form of arginase (ARG2), which hydrolyzes arginine into ornithine and urea, is induced upon obesity, and silencing or loss of ARG2 markedly suppresses PDA...
August 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/28808191/shunts-channels-and-lipoprotein-endosomal-traffic-a-new-model-of-cholesterol-homeostasis-in-the-hepatocyte
#19
Robert Scott Kiss, Allan Sniderman
The liver directs cholesterol metabolism in the organism. All the major fluxes of cholesterol within the body involve the liver: dietary cholesterol is directed to the liver; cholesterol from peripheral cells goes to the liver; the liver is a major site of cholesterol synthesis for the organism; cholesterol is secreted from the liver within the bile, within apoB lipoproteins and translocated to nascent HDL. The conventional model of cholesterol homeostasis posits that cholesterol from any source enters a common, rapidly exchangeable pool within the cell, which is in equilibrium with a regulatory pool...
January 19, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28807779/syringo-subarachnoid-shunt-for-the-treatment-of-persistent-syringomyelia-following-decompression-for-chiari-type-i-malformation-surgical-results
#20
Jehuda Soleman, Jonathan Roth, Andrea Bartoli, Daniel Rosenthal, Akiva Korn, Shlomi Constantini
BACKGROUND: Approximately 30% of patients treated by foramen magnum decompression (FMD) for Chiari I-associated-syringomyelia will show persistence, recurrence, or progression of the syrinx. OBJECTIVE: This study evaluates the clinical and radiological outcome of syringo-subarachnoid shunt (SSS) as the treatment for persistent syringomyelia after FMD. METHODS: Data was collected retrospectively. The primary outcome measurement was neurological function (assessed with the Modified Japanese Orthopedic Association (mJOA) scale)...
August 11, 2017: World Neurosurgery
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