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https://www.readbyqxmd.com/read/28527325/dyslipidemia-management-update
#1
REVIEW
Yingzi Chang, Jacques Robidoux
Association of hypercholesterolemia and atherosclerotic cardiovascular disease (ASCVD) is well established. Reducing low-density lipoprotein-cholesterol (LDL-C) and raising high-density lipoprotein-cholesterol (HDL-C) have been the therapeutic targets to reduce the risk of ASCVD. Cholesterol-lowering medications have been used to provide both primary and secondary prevention of ASCVD for many years by reducing the absorption and reabsorption, promoting excretion, or decreasing the synthesis of cholesterol. Within the past five years, several new classes of cholesterol-lowering drugs have been tested and approved for patients with hypercholesterolemia that are not well controlled by conventional therapy (ezetimibe, bile-acid sequestrants, and statins)...
May 17, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28527282/-determination-of-hla-a-b-and-drb1-polymorphism-in-brain-dead-organ-donors-representative-of-the-colombian-general-population-2007-2014
#2
Yazmin Rocío Arias, Karime Osorio-Arango, Brayan Bayona, Guadalupe Ercilla, Mauricio Beltrán-Durán
INTRODUCTION: Genes encoding for human leukocyte antigens (HLA) are highly polymorphic and of great importance in organ transplantation procedures, as determining allelic frequencies in defined populations is taken into account among the scientific criteria for organ allocation. OBJECTIVE: The objective of this study was to establish the antigen HLA-A, -B, and -DRB1 haplotype frequencies in organ donors representative of the Colombian population after brain death...
June 1, 2017: Biomédica: Revista del Instituto Nacional de Salud
https://www.readbyqxmd.com/read/28527239/the-structure-of-a-lair1-containing-human-antibody-reveals-a-novel-mechanism-of-antigen-recognition
#3
Fu-Lien Hsieh, Matthew K Higgins
Antibodies are critical components of the human adaptive immune system, providing versatile scaffolds to display diverse antigen binding surfaces. Nevertheless, most antibodies have similar architectures, with the variable immunoglobulin domains of the heavy and light chain each providing three hypervariable loops, which are varied to generate diversity. The recent identification of a novel class of antibody in humans from malaria endemic regions of Africa was therefore surprising as one hypervariable loop contains the entire collagen-binding domain of human LAIR1...
May 20, 2017: ELife
https://www.readbyqxmd.com/read/28527163/pharmacotherapy-of-insomnia-and-current-updates
#4
REVIEW
Arup Kumar Misra, Pramod Kumar Sharma
Insomnia is highly prevalent and is associated with a range of psychological, psychiatric, and medical conditions. Insomnia affects health by influencing cognitive, emotional and social functioning. Circadian and sleep homeostatic processes play an important role in insomnia development and its maintenance. Several efficacious treatments, both pharmacologic and non-pharmacologic, exist for the management of insomnia. Among non-pharmacologic treatments including stimulus control therapy, sleep restriction, relaxation, sleep hygiene and cognitive therapy have been shown to be efficacious...
April 2017: Journal of the Association of Physicians of India
https://www.readbyqxmd.com/read/28527149/characterisation-of-drug-related-problems-and-associated-factors-at-a-clinical-pharmacist-service-na%C3%A3-ve-hospital-in-northern-sweden
#5
Cecilia Peterson, Maria Gustafsson
BACKGROUND: Polypharmacy and increased sensitivity to side effects cause adverse drug events, drug-drug interactions and medication errors in the elderly. OBJECTIVE: The objective of this study was to investigate the prevalence and type of drug-related problems and associated factors among patients admitted to a clinical pharmacist service-naïve medical ward in an inland hospital in northern Sweden. METHODS: During September-November 2015 and February-April 2016, clinical pharmacists working as part of a ward team on the medical ward conducted 103 medication reviews...
May 19, 2017: Drugs—Real World Outcomes
https://www.readbyqxmd.com/read/28527142/temporal-and-spatial-features-of-selected-wastewater-marking-pharmaceuticals-and-potential-mechanisms-of-their-removal-from-urban-rivers
#6
Haidong Zhou, Yadan Wangjin, Jianbo Liu, Tianqi Ying, Yumei Xuan
The investigations on seasonal and spatial distribution of 12 selected wastewater-marking pharmaceuticals (WWMPs) belonging to different therapeutic classes were conducted in three major urban rivers of Yangpu District, Shanghai, East China. The potential mechanisms for the removal of WWMPs in the rivers were also experimentally investigated. The detection frequencies of most WWMPs were in the range of 56-100%, with the exception of clofibric acid, which was not detected during the storm events. The median concentrations ranged from not detected to 5821 ng/L (caffeine) and the maximum concentration was 8662 ng/L, found in caffeine...
May 19, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28526957/cytomorphology-review-of-100-newly-diagnosed-lower-risk-mds-patients-in-the-european-leukemianet-mds-eumds-registry-reveals-a-high-inter-observer-concordance
#7
Louise de Swart, Alex Smith, Marius MacKenzie, Argiris Symeonidis, Judith Neukirchen, Dana Mikulenková, Teresa Vallespí, Gina Zini, Malgorzata Paszkowska-Kowalewska, Anton Kruger, Leonie Saft, Pierre Fenaux, David Bowen, Eva Hellström-Lindberg, Jaroslav Čermák, Reinhard Stauder, Aurelia Tatic, Mette Skov Holm, Luca Malcovati, Krzysztof Mądry, Jackie Droste, Nicole Blijlevens, Theo de Witte, Ulrich Germing
The European LeukemiaNet MDS (EUMDS) registry is collecting data of myelodysplastic syndrome (MDS) patients belonging to the IPSS low or intermediate-1 category, newly diagnosed by local cytologists. The diagnosis of MDS can be challenging, and some data report inter-observer variability with regard to the assessment of the MDS subtype. In order to ensure that correct diagnoses were made by the participating centres, blood and bone marrow slides of 10% of the first 1000 patients were reviewed by an 11-person panel of cytomorphologists...
May 20, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28526869/blocking-of-carnitine-palmitoyl-transferase-1-potently-reduces-stress-induced-depression-in-rat-highlighting-a-pivotal-role-of-lipid-metabolism
#8
Anne Skøttrup Mørkholt, Ove Wiborg, Jette G K Nieland, Søren Nielsen, John Dirk Nieland
Major depressive disorder is a complex and common mental disease, for which the pathology has not been elucidated. The purpose of this study is to provide knowledge about the importance of mitochondrial dysfunction, dysregulated lipid metabolism and inflammation. Mitochondrial carnitine palmitoyl transferase 1a (CPT1a) is a key molecule involved in lipid metabolism and mutations in CPT1a causing reduced function is hypothesized to have a protective role in the development of depression. Moreover, CPT1a is found to be upregulated in suicide patients with history of depression...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28526830/computationally-driven-engineering-of-sublattice-ordering-in-a-hexagonal-alhfsctizr-high-entropy-alloy
#9
Lukasz Rogal, Piotr Bobrowski, Fritz Körmann, Sergiy Divinski, Frank Stein, Blazej Grabowski
Multi-principle element alloys have enormous potential, but their exploration suffers from the tremendously large range of configurations. In the last decade such alloys have been designed with a focus on random solid solutions. Here we apply an experimentally verified, combined thermodynamic and first-principles design strategy to reverse the traditional approach and to generate a new type of hcp Al-Hf-Sc-Ti-Zr high entropy alloy with a hitherto unique structure. A phase diagram analysis narrows down the large compositional space to a well-defined set of candidates...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28526770/therapeutic-ige-antibodies-harnessing-a-macrophage-mediated-immune-surveillance-mechanism-against-cancer
#10
REVIEW
Sophia N Karagiannis, Debra H Josephs, Heather J Bax, James F Spicer
IgG monoclonal antibodies have made significant contributions to cancer therapy, but suffer from several limitations that restrict their effectiveness in unleashing host immune system components against tumors. The development of monoclonal antibodies of an alternative class, namely IgE, may offer enhanced immune surveillance and superior effector cell potency against cancer cells. In our recent article, we elaborate our proof-of-concept studies of a mouse/human chimeric IgE antibody (MOv18 IgE), which is specific for the cancer-associated antigen folate receptor alpha...
May 19, 2017: Cancer Research
https://www.readbyqxmd.com/read/28526749/the-origin-and-evolution-of-human-glutaminases-and-their-atypical-c-terminal-ankyrin-repeats
#11
Camila Cristina Pascoal, Zeyaul Islam, Douglas Adamoski, Igor Monteze Ferreira, Ricardo Diogo Righetto, Jefferson Bettini, Rodrigo Villares Portugal, Wyatt W Yue, Ana Gonzalez, Sandra Martha Gomes Dias, Andre Luis Berteli Ambrosio
On the basis of tissue-specific enzyme activity and inhibition by catalytic products, Hans Krebs first demonstrated the existence of multiple glutaminases in mammals. Currently, two human genes are known to encode at least four glutaminase isoforms. However, the phylogeny of these medically relevant enzymes remains unclear, prompting us to investigate their origin and evolution. Using prokaryotic and eukaryotic glutaminase sequences, we built a phylogenetic tree whose topology suggested that the multidomain architecture was inherited from bacterial ancestors, probably simultaneously with the hosting of the proto-mitochondrion endosymbiont...
May 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28526744/combining-properties-of-different-classes-of-pi3k%C3%AE-inhibitors-to-understand-molecular-features-that-confer-selectivity
#12
Grace Q Gong, Jackie D Kendall, James Mj Dickson, Gordon W Rewcastle, Christina M Buchanan, William A Denny, Peter R Shepherd, Jack U Flanagan
Phosphoinositide 3-kinases (PI3K) are major regulators of many cellular functions, and hyperactivation of PI3K cell signalling pathways is a major target for anticancer drug discovery. PI3Kα is the isoform most implicated in cancer, and our aim is to selectively inhibit this isoform, which may be more beneficial than concurrent inhibition of all Class I PI3Ks. We have used structure-guided design to merge high selectivity and high affinity characteristics found in existing compounds. Molecular docking including the prediction of water-mediated interactions, was used to model interactions between the ligands and the PI3Kα affinity pocket...
May 19, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28526717/major-contribution-of-the-3-6-7-class-of-trpc-channels-to-myocardial-ischemia-reperfusion-and-cellular-hypoxia-reoxygenation-injuries
#13
Xiju He, Shoutian Li, Benju Liu, Sebastian Susperreguy, Karina Formoso, Jinghong Yao, Jinsong Kang, Anbing Shi, Lutz Birnbaumer, Yanhong Liao
The injury phase after myocardial infarcts occurs during reperfusion and is a consequence of calcium release from internal stores combined with calcium entry, leading to cell death by apoptopic and necrotic processes. The mechanism(s) by which calcium enters cells has(ve) not been identified. Here, we identify canonical transient receptor potential channels (TRPC) 3 and 6 as the cation channels through which most of the damaging calcium enters cells to trigger their death, and we describe mechanisms activated during the injury phase...
May 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28526695/-thinking-ethics-a-novel-pilot-proof-of-concept-program-of-integrating-ethics-into-the-physiology-curriculum-in-south-india
#14
Savitha D, Manjulika Vaz, Mario Vaz
Integrating medical ethics into the physiology teaching-learning program has been largely unexplored in India. The objective of this exercise was to introduce an interactive and integrated ethics program into the Physiology course of first-year medical students and to evaluate their perceptions. Sixty medical students (30 men, 30 women) underwent 11 sessions over a 7-mo period. Two of the Physiology faculty conducted these sessions (20-30 min each) during the routine physiology (theory/practicals) classes that were of shorter duration and could, therefore, accommodate the discussion of related ethical issues...
June 1, 2017: Advances in Physiology Education
https://www.readbyqxmd.com/read/28526548/at-the-nexus-of-antibiotics-and-metals-the-impact-of-cu-and-zn-on-antibiotic-activity-and-resistance
#15
REVIEW
Keith Poole
Environmental influences on antibiotic activity and resistance can wreak havoc with in vivo antibiotic efficacy and, ultimately, antimicrobial chemotherapy. In nature, bacteria encounter a variety of metal ions, particularly copper (Cu) and zinc (Zn), as contaminants in soil and water, as feed additives in agriculture, as clinically-used antimicrobials, and as components of human antibacterial responses. Importantly, there is a growing body of evidence for Cu/Zn driving antibiotic resistance development in metal-exposed bacteria, owing to metal selection of genetic elements harbouring both metal and antibiotic resistance genes, and metal recruitment of antibiotic resistance mechanisms...
May 16, 2017: Trends in Microbiology
https://www.readbyqxmd.com/read/28526426/the-effects-of-troglitazone-on-ampk-in-hepg2-cells
#16
Katherine M Allen, Kimberly A Coughlan, Fabliha N Mahmood, Rudy J Valentine, Neil B Ruderman, Asish K Saha
AMP-activated protein kinase (AMPK) is an enzyme crucial in cellular metabolism found to be inhibited in many metabolic diseases including type 2 diabetes. Thiazolidinediones (TZDs) are a class of anti-diabetic drug known to activate AMPK through increased phosphorylation at Thr(172), however there has been no research to date on whether they have any effect on inhibition of AMPK's lesser known site of inhibition, Ser(485/491). HepG2 cells were treated with troglitazone and phosphorylation of AMPK was found to increase at both Thr(172) and Ser(485) in a dose- and time-dependent manner...
May 16, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28526414/a-novel-sirt1-inhibitor-4bb-induces-apoptosis-in-hct116-human-colon-carcinoma-cells-partially-by-activating-p53
#17
Ananga Ghosh, Amrita Sengupta, Guru Pavan Kumar Seerapu, Ali Nakhi, E V Venkat Shivaji Ramarao, Navneet Bung, Gopalakrishnan Bulusu, Manojit Pal, Devyani Haldar
The NAD+-dependent protein deacetylase SIRT1 has emerged as an important target for epigenetic therapeutics of colon cancer as its increased expression is associated with cancer progression. Additionally, SIRT1 represses p53 function via deacetylation, promoting tumor growth. Therefore, inhibition of SIRT1 is of great therapeutic interest for the treatment of colon cancer. Here, we report discovery of a novel quinoxaline based small molecule inhibitor of human SIRT1, 4bb, investigated its effect on viability of colon cancer cells and molecular mechanism of action...
May 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28526407/sirtuin-inhibition-leads-to-autophagy-and-apoptosis-in-porcine-preimplantation-blastocysts
#18
Min Gyeong Kim, Duk Hyoun Kim, Hye Ran Lee, Jun Sung Lee, Su Jin Jin, Hoon Taek Lee
Sirtuins are nicotinamide adenine dinucleotide dependent class III histone deacetylase proteins that play a crucial role in several cellular processes, including DNA repair, apoptosis, and lifespan. Previous studies have shown that sirtuin inhibition leads to embryonic developmental arrest and oxidative stress in porcine and murine. However, sirtuin-mediated mechanisms have not been examined in porcine preimplantation blastocysts. We therefore investigated the relationship between sirtuins and autophagy. Embryos were cultured with 100 μM sirtinol (SIRT1/2 inhibitor) in NCSU-23 media after in vitro fertilization...
May 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28526399/evaluation-of-the-effectiveness-of-chronic-antidepressant-drug-treatments-in-the-hippocampal-mitochondria-a-proteomic-study-in-an-animal-model-of-depression
#19
Katarzyna Głombik, Aneta Stachowicz, Ewa Trojan, Rafał Olszanecki, Joanna Ślusarczyk, Maciej Suski, Katarzyna Chamera, Bogusława Budziszewska, Władysław Lasoń, Agnieszka Basta-Kaim
Several lines of evidence indicate that adverse experience in early life may be a triggering factor for disturbances in the brain mitochondrial proteins and lead to the development of depression in adulthood. On the other hand, little is known about the impact of chronic administration of various antidepressant drugs on the brain mitochondria, as a target for the pharmacotherapy of depression. The purpose of our study was to compare the impact of chronic treatment with two antidepressant drugs with different mechanisms of action, a tricyclic antidepressant (TCA), imipramine, and an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class, fluoxetine, on the mitochondria-enriched subproteome profile in the hippocampus of 3-month-old male rats following a prenatal stress procedure (an animal model of depression)...
May 16, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28526393/energy-drink-consumption-and-marketing-in-south-africa
#20
Nicholas Stacey, Corné van Walbeek, Mashekwa Maboshe, Aviva Tugendhaft, Karen Hofman
Energy drinks are a fast-growing class of beverage containing high levels of caffeine and sugar. Advertising and marketing have been key to their growth in South Africa. This paper documents trends in energy drink consumption and energy drink advertising, and examines the relationship between exposure to energy drink advertising and consumption. Logistic regressions were estimated of categories of energy drink consumption on individual characteristics, as well as exposure to energy drink advertising. Exposure to advertising is measured by reported viewing of channels high in energy drink advertising...
May 16, 2017: Preventive Medicine
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