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https://www.readbyqxmd.com/read/28541820/assessment-of-the-effects-of-2-methoxyethyl-antisense-oligonucleotides-on-platelet-count-in-cynomolgus-nonhuman-primates
#1
Scott P Henry, Padmakumar Narayanan, Lijiang Shen, Sanjay Bhanot, Husam S Younis, Sebastien A Burel
Decreases in platelet (PLT) counts observed in nonhuman primates (NHPs) given 2'-O-methoxyethyl modified antisense inhibitors (2'-MOE ASOs) have been reported, but the incidence and severity of the change vary considerably between sequences, studies, and animals. This article will broadly illustrate the spectrum of effects on PLT count in NHPs. From queries of an NHP safety database representing over 102 independent 2'-MOE ASOs, from 61 studies and >2200 NHPs, two patterns of PLT changes emerged. The first is a consistent and reproducible decrease in group mean values, observed with about 30% of the compounds, in which PLT count typically remains ≥150K cells/μL...
May 25, 2017: Nucleic Acid Therapeutics
https://www.readbyqxmd.com/read/28539463/braf-fusion-as-a-novel-mechanism-of-acquired-resistance-to-vemurafenib-in-braf-v600e-mutant-melanoma
#2
Atul Kulkarni, Husam Al-Hraishawi, Srilatha Simhadri, Kim M Hirshfield, Suzie Chen, Sharon R Pine, Chandrika Jeyamohan, Levi Sokol, Siraj M Ali, Man Lung Teo, Eileen White, Lorna Rodriguez-Rodriguez, Janice M Mehnert, Shridar Ganesan
Many patients with BRAF (V)(600E) mutant melanoma treated with BRAF inhibitors experience a rapid response, but ultimately develop resistance. Insight into the mechanism of resistance is critical for development of more effective treatment strategies. <br /><br />Experimental Design: Comprehensive genomic profiling of serial biopsies was performed in a patient with a BRAF(V600E) mutant metastatic melanoma who developed resistance to vemurafenib. An AGAP3-BRAF fusion gene, identified in the vemurafenib-resistant tumor, was expressed in BRAF(V600E) melanoma cell lines and its effect on drug sensitivity was evaluated...
May 24, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28499912/cyclophosphamide-and-acrolein-induced-oxidative-stress-leading-to-deterioration-of-metaphase-ii-mouse-oocyte-quality
#3
Roohi Jeelani, Sana N Khan, Faten Shaeib, Hamid-Reza Kohan-Ghadr, Sarah R Aldhaheri, Tohid Najafi, Mili Thakur, Robert Morris, Husam M Abu-Soud
Cyclophosphamide (CTX) is a chemotherapeutic agent widely used to treat ovarian, breast, and hematological cancers as well as autoimmune disorders. Such chemotherapy is associated with reproductive failure and premature ovarian insufficiency. The mechanism by which CTX and or its main metabolite, acrolein, affect female fertility remains unclear, but it is thought to be caused by an overproduction of reactive oxygen species (ROS). Here, we investigated the effect of CTX on metaphase II mouse oocytes obtained from treated animal (120mg/kg, 24 h of single treatment), and oocytes directly exposed to increasing concentrations of CTX and acrolein (n=480; 0, 5, 10, 25, 50, and 100μM) with and without cumulus cells (CCs) for 45min which correlates to the time of maximum peak plasma concentrations after administration...
May 9, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28491729/late-presentation-of-constrictive-pericarditis-after-limited-epicardial-ablation-for-inappropriate-sinus-tachycardia
#4
Adam Oesterle, Amita Singh, Husam Balkhy, Aliya N Husain, Deborah Moyer, Roderick Tung, Hemal M Nayak
No abstract text is available yet for this article.
September 2016: HeartRhythm Case Reports
https://www.readbyqxmd.com/read/28482292/new-drugs-for-the-treatment-of-mycobacterium-tuberculosis-infection
#5
REVIEW
Manaf AlMatar, Husam AlMandeal, Işıl Var, Begüm Kayar, Fatih Köksal
Tuberculosis presents a grave challenge to health, globally instigating 1.5 million mortalities each year. Following the breakthrough of first-line anti-TB medication, the number of mortalities reduced greatly; nonetheless, the swift appearance of tuberculosis which was drug-resistant, as well as the capability of the bacterium to survive and stay dormant are a considerable problem for public health. In order to address this issue, several novel possible candidates for tuberculosis therapy have been subjected to clinical trials of late...
May 5, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28480708/spin-filtering-in-epitaxial-spinel-films-with-nanoscale-phase-separation
#6
Peng Li, Chuan Xia, Jun Li, Zhiyong Zhu, Yan Wen, Qiang Zhang, Junwei Zhang, Yong Peng, Husam N Alshareef, Xixiang Zhang
The coexistence of ferromagnetic metallic phase and antiferromagnetic insulating phase in nanoscaled inhomogeneous perovskite oxides accounts for the colossal magnetoresistance. Although the model of spin-polarized electron transport across antiphase boundaries has been commonly employed to account for large magnetoresistance (MR) in ferrites, the magnetic anomalies, the two magnetic phases and enhanced molecular moment, are still unresolved. We observed a sizable MR in epitaxial spinel films (NiCo2O4-δ) that is much larger than that commonly observed in spinel ferrites...
May 10, 2017: ACS Nano
https://www.readbyqxmd.com/read/28437539/safety-and-efficacy-of-antiviral-therapy-for-prevention-of-cytomegalovirus-reactivation-in-immunocompetent-critically-ill-patients-a-randomized-clinical-trial
#7
Nicholas J Cowley, Andrew Owen, Sarah C Shiels, Joanne Millar, Rebecca Woolley, Natalie Ives, Husam Osman, Paul Moss, Julian F Bion
Importance: Latent cytomegalovirus (CMV) infection is present in more than half the adult population, and a viral reactivation (ie, when the virus becomes measurable in body fluids such as blood) can occur in up to one-third of these individuals during episodes of critical illness. Objective: To determine whether antiviral therapy is safe and effective for preventing CMV reactivation in a general population of critically ill patients. Design, Setting, and Participants: A single-center, open-label, randomized, controlled clinical trial recruited 124 CMV-seropositive patients undergoing mechanical ventilation for at least 24 hours in the intensive care unit between January 1, 2012, and January 31, 2014...
April 24, 2017: JAMA Internal Medicine
https://www.readbyqxmd.com/read/28430538/biophysical-comparison-of-diphtheria-and-tetanus-toxins-with-the-formaldehyde-detoxified-toxoids-the-main-components-of-diphtheria-and-tetanus-vaccines
#8
Husam Alsarraf, Emil Dedic, Morten J Bjerrum, Ole Østergaard, Max Per Kristensen, Jesper W Petersen, René Jørgensen
No abstract text is available yet for this article.
April 21, 2017: Virulence
https://www.readbyqxmd.com/read/28424290/skin-derived-precursors-from-human-subjects-with-type-2-diabetes-yield-dysfunctional-vascular-smooth-muscle-cells
#9
Sarah Katherina Steinbach, Terrence M Yau, Maral Ouzounian, Husam Abdel-Qadir, Mark Chandy, Thomas Waddell, Mansoor Husain
Objective: Few methods enable molecular and cellular studies of vascular aging or type-2 diabetes (T2D). Here we report a new approach to studying human vascular smooth muscle cell (VSMC) pathophysiology by examining VSMCs differentiated from progenitors found in skin. Approach and Results: Skin-derived precursors (SKPs) were cultured from biopsies (N=164, ~1 cm(2)) taken from the edges of surgical incisions of older adults (N=158; males 72%; mean age 62.7±13 years) undergoing cardiothoracic surgery, and differentiated into VSMCs at high efficiency (>80% yield)...
April 19, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28401166/hypodontia-an-update-on-its-etiology-classification-and-clinical-management
#10
REVIEW
Azza Husam Al-Ani, Joseph Safwat Antoun, William Murray Thomson, Tony Raymond Merriman, Mauro Farella
Hypodontia, or tooth agenesis, is the most prevalent craniofacial malformation in humans. It may occur as part of a recognised genetic syndrome or as a nonsyndromic isolated trait. Excluding third molars, the reported prevalence of hypodontia ranges from 1.6 to 6.9%, depending on the population studied. Most affected individuals lack only one or two teeth, with permanent second premolars and upper lateral incisors the most likely to be missing. Both environmental and genetic factors are involved in the aetiology of hypodontia, with the latter playing a more significant role...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28365690/changes-in-ip3-receptor-expression-and-function-in-aortic-smooth-muscle-of-atherosclerotic-mice
#11
Marie-Ann Ewart, Azizah Ugusman, Anisha Vishwanath, Tarek A M Almabrouk, Husam Alganga, Omar J Katwan, Pavlina Hubanova, Susan Currie, Simon Kennedy
Peroxynitrite is an endothelium-independent vasodilator that induces relaxation via membrane hyperpolarization. The activation of IP3 receptors triggers the opening of potassium channels and hyperpolarization. Previously we found that relaxation to peroxynitrite was maintained during the development of atherosclerosis due to changes in the expression of calcium-regulatory proteins. In this study we investigated: (1) the mechanism of peroxynitrite-induced relaxation in the mouse aorta, (2) the effect of atherosclerosis on relaxation to peroxynitrite and other vasodilators, and (3) the effect of atherosclerosis on the expression and function of the IP3 receptor...
2017: Journal of Vascular Research
https://www.readbyqxmd.com/read/28362120/traumatic-brain-injury-rehabilitation-in-riyadh-saudi-arabia-time-to-rehabilitation-admission-length-of-stay-and-functional-outcome
#12
Hazem Qannam, Husam Mahmoud, W Ben Mortenson
OBJECTIVES: (1) Describe trends in time to rehabilitation admission and rehabilitation length of stay (LOS), (2) compare functional independence at discharge from rehabilitation between patients who arrived directly from acute care versus those from elsewhere and (3) identify independent predictors of functional outcomes following rehabilitation. SETTING: Traumatic brain injuries rehabilitation unit of King Fahad Medical City, Riyadh, Saudi Arabia. METHODS: We collected information on time from injury to rehabilitation admission, rehabilitation LOS, functional independence measure (FIM) score (admission and discharge) and demographic variables for 66 patients who arrived to rehabilitation from acute care and 142 patients who arrived from elsewhere...
March 31, 2017: Brain Injury: [BI]
https://www.readbyqxmd.com/read/28361814/macronutrient-intake-insulin-secretion-oxidative-stress-inflammation-clinico-pathological-implications
#13
EDITORIAL
Paresh Dandona, Husam Ghanim, Ajay Chaudhuri, Priya Mohanty
No abstract text is available yet for this article.
November 2016: Indian Journal of Medical Research
https://www.readbyqxmd.com/read/28345211/3d-echocardiographic-analysis-of-aortic-annulus-for-transcatheter-aortic-valve-replacement-using-novel-aortic-valve-quantification-software-comparison-with-computed-tomography
#14
Anuj Mediratta, Karima Addetia, Diego Medvedofsky, Robert J Schneider, Eric Kruse, Atman P Shah, Sandeep Nathan, Jonathan D Paul, John E Blair, Takeyoshi Ota, Husam H Balkhy, Amit R Patel, Victor Mor-Avi, Roberto M Lang
BACKGROUND: With the increasing use of transcatheter aortic valve replacement (TAVR) in patients with aortic stenosis (AS), computed tomography (CT) remains the standard for annulus sizing. However, 3D transesophageal echocardiography (TEE) has been an alternative in patients with contraindications to CT. We sought to (1) test the feasibility, accuracy, and reproducibility of prototype 3DTEE analysis software (Philips) for aortic annular measurements and (2) compare the new approach to the existing echocardiographic techniques...
May 2017: Echocardiography
https://www.readbyqxmd.com/read/28331195/galactose-and-its-metabolites-deteriorate-metaphase-ii-mouse-oocyte-quality-and-subsequent-embryo-development-by-disrupting-the-spindle-structure
#15
Mili Thakur, Faten Shaeib, Sana N Khan, Hamid-Reza Kohan-Ghadr, Roohi Jeelani, Sarah R Aldhaheri, Bernard Gonik, Husam M Abu-Soud
Premature ovarian insufficiency (POI) is a frequent long-term complication of classic galactosemia. The majority of women with this disorder develop POI, however rare spontaneous pregnancies have been reported. Here, we evaluate the effect of D-galactose and its metabolites, galactitol and galactose 1-phosphate, on oocyte quality as well as embryo development to elucidate the mechanism through which these compounds mediate oocyte deterioration. Metaphase II mouse oocytes (n = 240), with and without cumulus cells (CCs), were exposed for 4 hours to D-galactose (2 μM), galactitol (11 μM) and galactose 1-phosphate (0...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28304146/liraglutide-acutely-suppresses-glucagon-lipolysis-and-ketogenesis-in-type-1-diabetes
#16
Manisha Garg, Husam Ghanim, Nitesh D Kuhadiya, Kelly Green, Jeanne Hejna, Sanaa Abuaysheh, Barrett Torre, Manav Batra, Antoine Makdissi, Ajay Chaudhuri, Paresh Dandona
In view of the occurrence of diabetic ketoacidosis associated with the use of sodium-glucose transport protein-2 (SGLT2) inhibitors in patients with type 1 diabetes (T1DM) and the relative absence of this complication in patients treated with liraglutide in spite of reductions in insulin doses, we investigated the effect of liraglutide on ketogenesis. Twenty-six patients with inadequately controlled T1DM were randomly divided into two groups of 13 patients each. After an overnight fast, patients were injected, subcutaneously, with either liraglutide 1...
March 17, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28291623/bmi-is-inversely-correlated-to-the-risk-of-mortality-in-patients-with-type-2-diabetes-hospitalized-for-acute-heart-failure-findings-from-the-gulf-acute-heart-failure-gulf-care-registry
#17
Charbel Abi Khalil, Kadhim Sulaiman, Rajvir Singh, Amin Jayyousi, Nidal Asaad, Khalid F AlHabib, Alawi Alsheikh-Ali, Mohammed Al-Jarallah, Bassam Bulbanat, Wael AlMahmeed, Soha Dargham, Mustafa Ridha, Nooshin Bazargani, Haitham Amin, Ahmed Al-Motarreb, Husam AlFaleh, Abdelfatah Elasfar, Prashanth Panduranga, Jassim Al Suwaidi
BACKGROUND: A U-shaped relationship has been reported between BMI and cardiovascular events among patients with acute heart failure (AHF). We hypothesized that an obesity paradox also governs the relationship between BMI and mortality in patients with type 2 diabetes (T2D) and AHF. METHODS: We studied 3-month and 12-month mortality in patients with T2D hospitalized for AHF according to 5 BMI categories: Underweight (<20kg/m(2)), normal weight (referent group, 20-24...
February 27, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28277246/robotic-mitral-valve-repair-with-right-ventricular-pacing-induced-ventricular-fibrillatory-arrest
#18
Andrew Hollatz, Husam H Balkhy, Mark A Chaney, Peter J Neuburger, Rebecca M Gerlach, T Sloane Guy
No abstract text is available yet for this article.
June 18, 2016: Journal of Cardiothoracic and Vascular Anesthesia
https://www.readbyqxmd.com/read/28165338/the-chromatin-remodeling-factor-chd7-controls-cerebellar-development-by-regulating-reelin-expression
#19
Danielle E Whittaker, Kimberley L H Riegman, Sahrunizam Kasah, Conor Mohan, Tian Yu, Blanca Pijuan Sala, Husam Hebaishi, Angela Caruso, Ana Claudia Marques, Caterina Michetti, María Eugenia Sanz Smachetti, Apar Shah, Mara Sabbioni, Omer Kulhanci, Wee-Wei Tee, Danny Reinberg, Maria Luisa Scattoni, Holger Volk, Imelda McGonnell, Fiona C Wardle, Cathy Fernandes, M Albert Basson
The mechanisms underlying the neurodevelopmental deficits associated with CHARGE syndrome, which include cerebellar hypoplasia, developmental delay, coordination problems, and autistic features, have not been identified. CHARGE syndrome has been associated with mutations in the gene encoding the ATP-dependent chromatin remodeler CHD7. CHD7 is expressed in neural stem and progenitor cells, but its role in neurogenesis during brain development remains unknown. Here we have shown that deletion of Chd7 from cerebellar granule cell progenitors (GCps) results in reduced GCp proliferation, cerebellar hypoplasia, developmental delay, and motor deficits in mice...
March 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28150382/making-models-to-simulate-testicular-swellings
#20
Piyush B Sarmah, Bhupendra D Sarmah, Husam Ibrahim, Jonathan Panting
BACKGROUND: Testicular examination and the recognition of common scrotal swellings is a key clinical skill that is difficult to teach undergraduates because of its intimate nature. A novel approach for this topic was prompted by the description of handmade models in the medical literature to teach anatomical knowledge and clinical skills. METHODS: Affordable low-cost materials were purchased and assembled to form six models replicating key scrotal pathologies: epididymal cyst, epididymitis, hydrocoele, inguinoscrotal hernia, testicular tumour and varicocoele...
February 2, 2017: Clinical Teacher
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