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https://www.readbyqxmd.com/read/29228202/activity-of-ceftazidime-avibactam-against-problem-enterobacteriaceae-and-pseudomonas-aeruginosa-in-the-uk-2015-16
#1
David M Livermore, Danièle Meunier, Katie L Hopkins, Michel Doumith, Robert Hill, Rachel Pike, Peter Staves, Neil Woodford
Background: Ceftazidime/avibactam combines an established oxyimino-cephalosporin with the first diazabicyclooctane β-lactamase inhibitor to enter clinical use. We reviewed its activity against Gram-negative isolates, predominantly from the UK, referred for resistance investigation in the first year of routine testing, beginning in July 2015. Methods: Isolates were as received from referring laboratories; there is a bias to submit those with suspected carbapenem resistance...
December 8, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29216806/an-industry-update-the-latest-developments-in-therapeutic-delivery
#2
Iain Simpson
This industry update covers the period from 1 September through 30 September 2017, and is based on information sourced from company press releases, scientific literature, patents and various news websites. The month saw the US FDA approve three new molecular entities, Aliqopa (copanlisib dihydrochloride) (Bayer Healthcare); Solosec (secnidazole) (Symbiomix Therapeutics) and Verzenio (abemaciclib) (Eli Lilly and Co). Intarcia Therapeutics Inc. has its application for approval of a novel drug device combination of exenatide for the treatment of diabetes rejected by FDA but said that it will work to address the concerns and refile the application...
January 2018: Therapeutic Delivery
https://www.readbyqxmd.com/read/29194564/oxaliplatin-induced-enteric-neuronal-loss-and-intestinal-dysfunction-is-prevented-by-co-treatment-with-bgp-15
#3
Rachel M McQuade, Vanesa Stojanovska, Rhian Stavely, Cara Timpani, Aaron C Petersen, Raquel Abalo, Joel C Bornstein, Emma Rybalka, Kulmira Nurgali
BACKGROUND AND PURPOSE: Gastrointestinal side-effects of chemotherapy are under-recognised clinical hurdle leading to dose reduction, delays and cessation of treatment, presenting a constant challenge for efficient and tolerable anti-cancer treatment. We have previously found that oxaliplatin treatment results in intestinal dysfunction, oxidative stress and loss of enteric neurons. BGP-15 is a novel cytoprotective compound with potential HSP72 co-inducing and PARP inhibiting properties...
November 30, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29175203/effects-of-bilingualism-on-white-matter-integrity-in-older-adults
#4
John A E Anderson, John G Grundy, Jaisalmer De Frutos, Ryan M Barker, Cheryl Grady, Ellen Bialystok
Bilingualism can delay the onset of dementia symptoms and has thus been characterized as a mechanism for cognitive or brain reserve, although the origin of this reserve is unknown. Studies with young adults generally show that bilingualism is associated with a strengthening of white matter, but there is conflicting evidence for how bilingualism affects white matter in older age. Given that bilingualism has been shown to help stave off the symptoms of dementia by up to four years, it is crucial that we clarify the mechanism underlying this reserve...
November 22, 2017: NeuroImage
https://www.readbyqxmd.com/read/29164103/the-human-antimicrobial-peptides-dermcidin-and-ll-37-show-novel-distinct-pathways-in-membrane-interactions
#5
REVIEW
Kornelius Zeth, Enea Sancho-Vaello
Mammals protect themselves from inflammation triggered by microorganisms through secretion of antimicrobial peptides (AMPs). One mechanism by which AMPs kill bacterial cells is perforating their membranes. Membrane interactions and pore formation were investigated for α-helical AMPs leading to the formulation of three basic mechanistic models: the barrel stave, toroidal, and carpet model. One major drawback of these models is their simplicity. They do not reflect the real in vitro and in vivo conditions. To challenge and refine these models using a structure-based approach we set out to investigate how human cathelicidin (LL-37) and dermcidin (DCD) interact with membranes...
2017: Frontiers in Chemistry
https://www.readbyqxmd.com/read/29156677/overcoming-resistance-to-single-agent-therapy-for-oncogenic-braf-gene-fusions-via-combinatorial-targeting-of-mapk-and-pi3k-mtor-signaling-pathways
#6
Payal Jain, Amanda Silva, Harry J Han, Shih-Shan Lang, Yuankun Zhu, Katie Boucher, Tiffany E Smith, Aesha Vakil, Patrick Diviney, Namrata Choudhari, Pichai Raman, Christine M Busch, Tim Delaney, Xiaodong Yang, Aleksandra K Olow, Sabine Mueller, Daphne Haas-Kogan, Elizabeth Fox, Phillip B Storm, Adam C Resnick, Angela J Waanders
Pediatric low-grade gliomas (PLGGs) are frequently associated with activating BRAF gene fusions, such as KIAA1549-BRAF, that aberrantly drive the mitogen activated protein kinase (MAPK) pathway. Although RAF inhibitors (RAFi) have been proven effective in BRAF-V600E mutant tumors, we have previously shown how the KIAA1549-BRAF fusion can be paradoxically activated by RAFi. While newer classes of RAFi, such as PLX8394, have now been shown to inhibit MAPK activation by KIAA1549-BRAF, we sought to identify alternative MAPK pathway targeting strategies using clinically relevant MEK inhibitors (MEKi), along with potential escape mechanisms of acquired resistance to single-agent MAPK pathway therapies...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29129184/identifying-attributes-of-care-that-may-improve-cost-effectiveness-in-the-youth-mental-health-service-system
#7
Matthew P Hamilton, Sarah E Hetrick, Cathrine Mihalopoulos, David Baker, Vivienne Browne, Andrew M Chanen, Kerryn Pennell, Rosemary Purcell, Heather Stavely, Patrick D McGorry
OBJECTIVE: To identify attributes of youth mental health care for which there is evidence of potential cost-effectiveness. STUDY DESIGN: We performed a literature review of economic evaluations that examined both costs and outcomes for attributes of youth mental health care other than pharmacological or individual psychological therapies for full-threshold disorders. DATA SOURCES: We searched the United Kingdom National Health Service Economic Evaluations Database for evaluations published to the end of 2014; and MEDLINE, Google Scholar and the citation lists of relevant publications for peer-reviewed studies published in English since 1997...
November 20, 2017: Medical Journal of Australia
https://www.readbyqxmd.com/read/29129183/targeting-mental-health-care-attributes-by-diagnosis-and-clinical-stage-the-views-of-youth-mental-health-clinicians
#8
Matthew P Hamilton, Sarah E Hetrick, Cathrine Mihalopoulos, David Baker, Vivienne Browne, Andrew M Chanen, Kerryn Pennell, Rosemary Purcell, Heather Stavely, Patrick D McGorry
OBJECTIVES: To explore the potential utility of clinical stage and mental disorder categories as a basis for determining which attributes of youth mental health care should be offered to which groups of young people. METHODS: In June 2017, we conducted an online survey of youth mental health clinicians that collected information on the participants' background and areas of expertise, then presented vignettes describing young people with different stages of six mental disorders (disorder-based vignettes were matched to participants' area of expertise)...
November 20, 2017: Medical Journal of Australia
https://www.readbyqxmd.com/read/29122629/long-term-cilostazol-administration-prevents-age-related-decline-of-hippocampus-dependent-memory-in-mice
#9
Shuichi Yanai, Hideki Ito, Shogo Endo
Phosphodiesterases (PDEs) are enzymes that hydrolyze and inactivate 3', 5'-cyclic adenosine monophosphate (cAMP) and/or 3', 5'-cyclic guanosine monophosphate (cGMP). The regulation of intracellular signaling pathways mediated by cyclic nucleotides is imperative to synaptic plasticity and memory in animals. Because PDEs play an important role in this regulation, PDE inhibitors are considered as candidate compounds for treating cognitive and memory disorders. In the present study, we tested whether cilostazol, a selective PDE3 inhibitor, prevents the cognitive deterioration that occurs during the course of normal aging in mice...
November 6, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29081792/polymalic-acid-tritryptophan-copolymer-interacts-with-lipid-membrane-resulting-in-membrane-solubilization
#10
Hui Ding, Irving Fox, Rameshwar Patil, Anna Galstyan, Keith L Black, Julia Y Ljubimova, Eggehard Holler
Anionic polymers with membrane permeation functionalities are highly desirable for secure cytoplasmic drug delivery. We have developed tritryptophan containing copolymer (P/WWW) of polymalic acid (PMLA) that permeates membranes by a mechanism different from previously described PMLA copolymers of trileucine (P/LLL) and leucine ethyl ester (P/LOEt) that use the "barrel stave" and "carpet" mechanism, respectively. The novel mechanism leads to solubilization of membranes by forming copolymer "belts" around planar membrane "packages...
2017: Journal of Nanomaterials
https://www.readbyqxmd.com/read/29030954/an-international-investigation-into-ab-plasma-administration-in-hospitals-how-many-ab-plasma-units-were-infused-the-habswin-study
#11
Michelle P Zeller, Rebecca Barty, Nancy M Dunbar, Allahna Elahie, Peter Flanagan, Henk Garritsen, José Mauro Kutner, Monica B Pagano, Ryszard Pogłód, Thomas S Rogers, Julie Staves, Maria van Wordragen-Vlaswinkel, Jaap Jan Zwaginga, Michael F Murphy, Nancy M Heddle, Mark H Yazer
BACKGROUND: Typical practice is to transfuse group-specific plasma units; however, there are situations where group AB plasma (universal donor) is issued to group A, B, or O recipients. If demand for group AB plasma exceeds collections, there is potential for shortage. This project explored the patterns of group AB plasma utilization at hospitals around the world. STUDY DESIGN AND METHODS: The study had two phases: a survey that inquired about hospital group AB plasma inventory, policies, and transfusion practices and a retrospective review of 2014 calendar year data where participants submitted information on plasma disposition including ABO group of unit and recipient, transfusion location, and select indications...
October 14, 2017: Transfusion
https://www.readbyqxmd.com/read/29030244/pore-formation-and-the-key-factors-in-antibacterial-activity-of-aurein-1-2-and-llaa-inside-lipid-bilayers-a-molecular-dynamics-study
#12
Nasim Cheraghi, Mahdieh Hosseini, Sarah Mohammadinejad
Aurein 1.2 and LLAA are two antimicrobial peptides with different antibacterial activities (LLAA>Aurein 1.2), though their amino acid sequences are similar. In this manuscript, we study the key features for the different antibacterial activities of these peptides using molecular dynamics simulation. We find that in water, both peptides become disordered and LLAA is observed to have higher water-solubility, a feature which may contribute to enhancing its propensity to disrupt the bilayer and thus higher activity...
October 10, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28994123/systematic-review-with-meta-analysis-rifaximin-for-the-prophylaxis-of-spontaneous-bacterial-peritonitis
#13
REVIEW
A Goel, U Rahim, L H Nguyen, C Stave, M H Nguyen
BACKGROUND: The primary and secondary prevention of spontaneous bacterial peritonitis (SBP) is recommended in high-risk patients with cirrhosis. Several studies evaluating the efficacy of rifaximin for SBP prophylaxis have yielded conflicting results. Rifaximin has the potential advantage of preventing bacterial overgrowth and translocation without the systemic side effects of broad-spectrum antibiotics. AIM: To evaluate the efficacy of rifaximin in the primary and secondary prevention of SBP...
December 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28883505/channel-formation-and-membrane-deformation-via-sterol-aided-polymorphism-of-amphidinol-3
#14
Masayuki Iwamoto, Ayumi Sumino, Eri Shimada, Masanao Kinoshita, Nobuaki Matsumori, Shigetoshi Oiki
Amphidinol 3 (AM3) is an anti-fungal polyene extracted from a marine dinoflagellate. Here, we examined the ion channel activity and membrane-embedded structure of AM3 using a lipid bilayer method and atomic force microscopy (AFM). AM3 exhibited large-conductance (~1 nS) and non-selective single-channel activity only when sterols were present in the membrane leaflet of the AM3-added side. The variable conductance suggests the formation of a multimeric barrel-stave pore. At high AM3 concentrations, giant-conductance "jumbo" channels (~40 nS) emerged...
September 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28840943/an-international-investigation-into-o-red-blood-cell-unit-administration-in-hospitals-the-group-o-utilization-patterns-group-study
#15
Michelle P Zeller, Rebecca Barty, Astrid Aandahl, Torunn O Apelseth, Jeannie Callum, Nancy M Dunbar, Allahna Elahie, Henk Garritsen, Helen Hancock, José Mauro Kutner, Belinda Manukian, Shuichi Mizuta, Makoto Okuda, Monica B Pagano, Ryszard Pogłód, Kylie Rushford, Kathleen Selleng, Claess Henning Sørensen, Ulrik Sprogøe, Julie Staves, Thorsten Weiland, Silvano Wendel, Erica M Wood, Leo van de Watering, Maria van Wordragen-Vlaswinkel, Alyssa Ziman, Jaap Jan Zwaginga, Michael F Murphy, Nancy M Heddle, Mark H Yazer
BACKGROUND: Transfusion of group O blood to non-O recipients, or transfusion of D- blood to D+ recipients, can result in shortages of group O or D- blood, respectively. This study investigated RBC utilization patterns at hospitals around the world and explored the context and policies that guide ABO blood group and D type selection practices. STUDY DESIGN AND METHODS: This was a retrospective study on transfusion data from the 2013 calendar year. This study included a survey component that asked about hospital RBC selection and transfusion practices and a data collection component where participants submitted information on RBC unit disposition including blood group and D type of unit and recipient...
October 2017: Transfusion
https://www.readbyqxmd.com/read/28796663/laboratory-animal-bite-anaphylaxis-a-national-survey-part-1-case-series-and-review-of-the-literature
#16
Gregg M Stave, Edward H Lee, Dennis J Darcey
OBJECTIVE: This study documents previously unreported cases of laboratory animal bite anaphylaxis in animal laboratory facilities in the United States. METHODS: An online survey was e-mailed to designated institutional officials at laboratory animal facilities identified by the National Institutes of Health Office of Laboratory Animal Welfare. RESULTS: One hundred ninety eight organizations responded and 15 organizations indicated that workers had experienced anaphylaxis following an animal bite...
August 2017: Journal of Occupational and Environmental Medicine
https://www.readbyqxmd.com/read/28782680/bilinguals-have-more-complex-eeg-brain-signals-in-occipital-regions-than-monolinguals
#17
John G Grundy, John A E Anderson, Ellen Bialystok
Brain signal complexity increases with development and is associated with better cognitive outcomes in older age. Research has also shown that bilinguals are able to stave off cognitive decline for longer periods of time than monolinguals, but no studies to date have examined whether bilinguals have more complex brain signals than monolinguals. Here we explored the hypothesis that bilingualism leads to greater brain signal complexity by examining multiscale entropy (MSE) in monolingual and bilingual young adults while EEG was recorded during a task-switching paradigm...
October 1, 2017: NeuroImage
https://www.readbyqxmd.com/read/28706386/alarming-emergence-molecular-characterization-and-outcome-of-blandm-1-in-patients-infected-with-multidrug-resistant-gram-negative-bacilli-in-a-tertiary-care-hospital
#18
Huma Naim, Meher Rizvi, Mohd Azam, Richa Gupta, Neelam Taneja, Indu Shukla, Haris M Khan
INTRODUCTION: This study was conducted to assess the prevalence of metallo-beta-lactamases (MBLs) in general and blaNDM-1 in particular. It also aimed at evaluating clinical characteristics and outcome in patients infected with MBLs. MATERIALS AND METHODS: A total of 116 carbapenem-resistant Gram-negative bacilli (CRGNB) were evaluated in the study. These CRGNB were tested for MBL production both phenotypically for MBLs and genotypically for blaNDM-1 gene by polymerase chain reaction (PCR)...
July 2017: Journal of Laboratory Physicians
https://www.readbyqxmd.com/read/28642990/how-health-humanities-will-save-the-life-of-the-humanities
#19
Craig M Klugman
In the last decade, the humanities have been shrinking in number of students, percent of faculty, and in number of degrees awarded. Humanities students also earn lower salaries than their STEM-prepared peers. At the same time, the health humanities have been in ascendance over the last fifteen years. The number of majors, minors and certificates has increased 266% in that time frame, attracting large numbers of students and preparing future patients, lay caregivers, and health care providers to interact with a complicated and dehumanized medical system...
December 2017: Journal of Medical Humanities
https://www.readbyqxmd.com/read/28637294/over-time-impacts-of-pictorial-health-warning-labels-and-their-differences-across-smoker-subgroups-results-from-adult-smokers-in-canada-and-australia
#20
Kamala Swayampakala, James F Thrasher, Hua-Hie Yong, Gera E Nagelhout, Lin Li, Ron Borland, David Hammond, Richard J O'Connor, James W Hardin
Introduction: This study examines patterns of change in different smoker subgroups' responses to new pictorial health warning labels (HWLs) over the initial, two year post-implementation period in Canada, where HWLs include package inserts with cessation messages, and Australia, where "plain" packaging (i.e., prohibition of brand imagery) was also implemented. Methods: Data were collected from online consumer panels in Canada (nsmokers=3,153; nobservations=5,826) and Australia (nsmokers=2,699; nobservations=5,818) from September 2012 to September 2014, with approximately 1,000 adult smokers surveyed in each country every four months, using replenishment to maintain sample size...
June 16, 2017: Nicotine & Tobacco Research: Official Journal of the Society for Research on Nicotine and Tobacco
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