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https://www.readbyqxmd.com/read/28109021/affordable-orphan-drugs-a-role-for-not-for-profit-organisations
#1
E H Davies, E Fulton, D Brook, D A Hughes
The success of the Regulation on Orphan Medicinal Products in the European Union is evidenced by the 127 orphan drugs that have had market authorisation since 2000. However the incentives aimed to stimulate research and development have had the unintended consequence of increasing drug cost, resulting in many orphan drugs not being cost-effective. Orphan drugs command an increasing share of the pharmaceutical market and account for a disproportionate amount of healthcare expenditure. Orphan drug ownership by socially motivated, not-for-profit organisations may facilitate access to more affordable orphan drugs, for the benefit of patients and healthcare systems alike...
January 20, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28108494/the-rich-club-organization-in-rat-functional-brain-network-to-balance-between-communication-cost-and-efficiency
#2
Xia Liang, Li-Ming Hsu, Hanbing Lu, Akira Sumiyoshi, Yong He, Yihong Yang
Network analyses of structural connectivity in the brain have highlighted a set of highly connected hubs that are densely interconnected, forming a "rich-club" substrate in diverse species. Here, we demonstrate the existence of rich-club organization in functional brain networks of rats. Densely interconnected rich-club regions are found to be distributed in multiple brain modules, with the majority located within the putative default mode network. Rich-club members exhibit high wiring cost (as measured by connection distance) and high metabolic running cost (as surrogated by cerebral blood flow), which may have evolved to achieve high network communications to support efficient brain functions...
January 19, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28108395/temporal-orienting-precedes-intersensory-attention-and-has-opposing-effects-on-early-evoked-brain-activity
#3
Julian Keil, Ulrich Pomper, Nele Feuerbach, Daniel Senkowski
Intersensory attention (IA) describes the process of directing attention to a specific modality. Temporal orienting (TO) characterizes directing attention to a specific moment in time. Previously, studies indicated that these two processes could have opposite effects on early evoked brain activity. The exact time-course and processing stages of both processes are still unknown. In this human electroencephalography study, we investigated the effects of IA and TO on visuo-tactile stimulus processing within one paradigm...
January 17, 2017: NeuroImage
https://www.readbyqxmd.com/read/28108385/seeing-an-embodied-virtual-hand-is-analgesic-contingent-on-co-location
#4
Birgit Nierula, Matteo Martini, Marta Matamala-Gomez, Mel Slater, Maria V Sanchez-Vives
: Seeing one's own body has been reported to have analgesic properties. Analgesia has also been described when seeing an embodied virtual body co-located with the real one. However, there is a controversy regarding whether this effect holds true when seeing an illusory-owned body part, such as during the rubber-hand illusion. A critical difference between these paradigms is the distance between real and surrogate body part. Co-location of real arm and surrogate is possible in an immersive virtual environment, but not during illusory ownership of a rubber arm...
January 17, 2017: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/28108252/abnormalities-in-cortical-auditory-responses-in-children-with-central-auditory-processing-disorder
#5
Amineh Koravand, Benoît Jutras, Maryse Lassonde
The main objective of the present study was to identify markers of neural deficits in children with central auditory processing disorder (CAPD) by measuring latency and amplitude of the auditory cortical responses and mismatch negativity (MMN) responses. Passive oddball paradigms were used with nonverbal and verbal stimuli to record cortical auditory evoked potentials and MMN. Twenty-three children ages 9 to 12 participated in the study: 10 with normal hearing acuity as well as CAPD and 13 with normal hearing without CAPD...
January 17, 2017: Neuroscience
https://www.readbyqxmd.com/read/28108039/laryngeal-mask-airways-in-anaesthetised-infants-a-paradigm-shift
#6
John Fiadjoe, Ronald Litman
No abstract text is available yet for this article.
January 17, 2017: Lancet
https://www.readbyqxmd.com/read/28107511/environmental-enrichment-blunts-ethanol-consumption-after-restraint-stress-in-c57bl-6-mice
#7
Priscila Marianno, Karina Possa Abrahao, Rosana Camarini
Elevated alcohol intake after abstinence is a key feature of the addiction process. Some studies have shown that environmental enrichment (EE) affects ethanol intake and other reinforcing effects. However, different EE protocols may vary in their ability to influence alcohol consumption and stress-induced intake. The present study evaluated whether short (3 h) or continuous (24 h) EE protocols affect ethanol consumption after periods of withdrawal. Mice were challenged with stressful stimuli (24 h isolation and restraint stress) to evaluate the effects of stress on drinking...
2017: PloS One
https://www.readbyqxmd.com/read/28106686/response-to-comments-by-drs-hamaoka-and-beyea-on-the-birth-of-the-illegitimate-linear-no-threshold-model-an-invalid-paradigm-for-estimating-risk-following-low-dose-radiation-exposure
#8
Jeffry A Siegel, Bill Sacks, Charles W Pennington, James S Welsh
No abstract text is available yet for this article.
February 2017: American Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28106318/reduced-laser-evoked-potential-habituation-detects-abnormal-central-pain-processing-in-painful-radiculopathy-patients
#9
P Hüllemann, C von der Brelie, G Manthey, J Düsterhöft, A K Helmers, M Synowitz, R Baron
BACKGROUND: Repetitive painful laser stimuli lead to physiological laser-evoked potential (LEP) habituation, measurable by a decrement of the N2/P2 amplitude. The time course of LEP-habituation is reduced in the capsaicin model for peripheral and central sensitization and in patients with migraine and fibromyalgia. In the present investigation, we aimed to assess the time course of LEP-habituation in a neuropathic pain syndrome, i.e. painful radiculopathy. METHODS: At the side of radiating pain, four blocks of 25 painful laser stimuli each were applied to the ventral thigh at the L3 dermatome in 27 patients with painful radiculopathy...
January 20, 2017: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/28106280/erk1-directly-interacts-with-jnk1-leading-to-regulation-of-jnk1-c-jun-activity-and-cell-transformation
#10
Bong Seok Kang, Yoon Jin Hwang, Zigang Dong
ERK1 and ERK2 share a great deal of homology and have been presumed to have similar functions. Available antibodies recognize both isoforms making the elucidation of functional differences challenging. Mitogen-activated protein (MAP) kinase networks are commonly depicted in the literature as linear and sequential phosphorylation cascades; however, the activation of these pathways is not mutually exclusive. Little doubt exists that MAP kinases engage in crosstalk, but the extent or the direct effect of these "conversations" is unclear...
January 20, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28106161/cold-spells-and-ischaemic-sudden-cardiac-death-effect-modification-by-prior-diagnosis-of-ischaemic-heart-disease-and-cardioprotective-medication
#11
Niilo R I Ryti, Elina M S Mäkikyrö, Harri Antikainen, M Juhani Junttila, Eeva Hookana, Tiina M Ikäheimo, Marja-Leena Kortelainen, Heikki V Huikuri, Jouni J K Jaakkola
Sudden cardiac death (SCD) is the leading cause of death. The current paradigm in SCD requires the presence of an abnormal myocardial substrate and an internal or external transient factor that triggers cardiac arrest. Based on prior mechanistic evidence, we hypothesized that an unusually cold weather event (a cold spell) could act as an external factor triggering SCD. We tested potential effect modification of prior diagnoses and select pharmacological agents disrupting pathological pathways between cold exposure and death...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28106142/identification-of-lukpq-a-novel-equid-adapted-leukocidin-of-staphylococcus-aureus
#12
Gerrit Koop, Manouk Vrieling, Daniel M L Storisteanu, Laurence S C Lok, Tom Monie, Glenn van Wigcheren, Claire Raisen, Xiaoliang Ba, Nicholas Gleadall, Nazreen Hadjirin, Arjen J Timmerman, Jaap A Wagenaar, Heleen M Klunder, J Ross Fitzgerald, Ruth Zadoks, Gavin K Paterson, Carmen Torres, Andrew S Waller, Anette Loeffler, Igor Loncaric, Armando E Hoet, Karin Bergström, Luisa De Martino, Constança Pomba, Hermínia de Lencastre, Karim Ben Slama, Haythem Gharsa, Emily J Richardson, Edwin R Chilvers, Carla de Haas, Kok van Kessel, Jos A G van Strijp, Ewan M Harrison, Mark A Holmes
Bicomponent pore-forming leukocidins are a family of potent toxins secreted by Staphylococcus aureus, which target white blood cells preferentially and consist of an S- and an F-component. The S-component recognizes a receptor on the host cell, enabling high-affinity binding to the cell surface, after which the toxins form a pore that penetrates the cell lipid bilayer. Until now, six different leukocidins have been described, some of which are host and cell specific. Here, we identify and characterise a novel S...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28106098/social-models-enhance-apes-memory-for-novel-events
#13
Lauren H Howard, Katherine E Wagner, Amanda L Woodward, Stephen R Ross, Lydia M Hopper
Nonhuman primates are more likely to learn from the actions of a social model than a non-social "ghost display", however the mechanism underlying this effect is still unknown. One possibility is that live models are more engaging, drawing increased attention to social stimuli. However, recent research with humans has suggested that live models fundamentally alter memory, not low-level attention. In the current study, we developed a novel eye-tracking paradigm to disentangle the influence of social context on attention and memory in apes...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28106040/the-effects-of-prior-stress-on-anxiety-like-responding-to-intra-bnst-pituitary-adenylate-cyclase-activating-polypeptide-pacap-in-male-and-female-rats
#14
S Bradley King, Kim R Lezak, Micaela O'Reilly, Donna J Toufexis, William A Falls, Karen Braas, Victor May, Sayamwong E Hammack
Chronic or repeated exposure to stressful stimuli can result in several maladaptive consequences, including increased anxiety-like behaviors and altered peptide expression in anxiety-related brain structures. Among these structures, the bed nucleus of the stria terminalis (BNST) has been implicated in emotional behaviors as well as regulation of hypothalamic-pituitary-adrenal (HPA) axis activity. In male rodents, chronic variate stress (CVS) has been shown to increase BNST pituitary adenylate cyclase activating polypeptide (PACAP) and its cognate PAC1 receptor transcript, and BNST PACAP signaling may mediate the maladaptive changes associated with chronic stress...
January 20, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28105890/multitasking-during-degraded-speech-recognition-in-school-age-children
#15
Tina M Grieco-Calub, Kristina M Ward, Laurel Brehm
Multitasking requires individuals to allocate their cognitive resources across different tasks. The purpose of the current study was to assess school-age children's multitasking abilities during degraded speech recognition. Children (8 to 12 years old) completed a dual-task paradigm including a sentence recognition (primary) task containing speech that was either unprocessed or noise-band vocoded with 8, 6, or 4 spectral channels and a visual monitoring (secondary) task. Children's accuracy and reaction time on the visual monitoring task was quantified during the dual-task paradigm in each condition of the primary task and compared with single-task performance...
January 2017: Trends in Hearing
https://www.readbyqxmd.com/read/28105638/socioeconomic-disparities-financial-toxicity-and-opportunities-for-enhanced-system-efficiencies-for-patients-with-cancer
#16
Daniel E Abbott, Corrine L Voils, Deborah A Fisher, Caprice C Greenberg, Nasia Safdar
Cancer care continues to stress the US healthcare system with increases in life expectancy, cancer prevalence, and survivors' complex needs. These challenges are compounded by socioeconomic, racial, and cultural disparities that are associated with poor clinical outcomes. One innovative and resource-wise strategy to address this demand on the system is expanded use of telehealth. This paradigm has the potential to decrease healthcare and patient out-of-pocket costs and improve patient adherence to recommended treatment and/or surveillance...
January 20, 2017: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28105588/nogo-a-antibodies-for-progressive-multiple-sclerosis
#17
Benjamin V Ineichen, Patricia S Plattner, Nicolas Good, Roland Martin, Michael Linnebank, Martin E Schwab
Most of the current therapies, as well as many of the clinical trials, for multiple sclerosis (MS) target the inflammatory autoimmune processes, but less than 20% of all clinical trials investigate potential therapies for the chronic progressive disease stage of MS. The latter is responsible for the steadily increasing disability in many patients, and there is an urgent need for novel therapies that protect nervous system tissue and enhance axonal growth and/or remyelination. As outlined in this review, solid pre-clinical data suggest neutralization of the neurite outgrowth inhibitor Nogo-A as a potential new way to achieve both axonal and myelin repair...
January 19, 2017: CNS Drugs
https://www.readbyqxmd.com/read/28104892/mechanistic-basis-for-a-molecular-triage-reaction
#18
Sichen Shao, Monica C Rodrigo-Brenni, Maryann H Kivlen, Ramanujan S Hegde
Newly synthesized proteins are triaged between biosynthesis and degradation to maintain cellular homeostasis, but the decision-making mechanisms are unclear. We reconstituted the core reactions for membrane targeting and ubiquitination of nascent tail-anchored membrane proteins to understand how their fate is determined. The central six-component triage system is divided into an uncommitted client-SGTA complex, a self-sufficient targeting module, and an embedded but self-sufficient quality control module. Client-SGTA engagement of the targeting module induces rapid, private, and committed client transfer to TRC40 for successful biosynthesis...
January 20, 2017: Science
https://www.readbyqxmd.com/read/28104823/changing-paradigms-in-contrast-nephropathy
#19
EDITORIAL
Arnaldo Lopez-Ruiz, Kiran Chandrashekar, Luis A Juncos
No abstract text is available yet for this article.
January 19, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28104355/allopregnanolone-induces-state-dependent-fear-via-the-bed-nucleus-of-the-stria-terminalis
#20
Gillian M Acca, Abel S Mathew, Jingji Jin, Stephen Maren, Naomi Nagaya
Gonadal steroids and their metabolites have been shown to be important modulators of emotional behavior. Allopregnanolone (ALLO), for example, is a metabolite of progesterone that has been linked to anxiety-related disorders such as posttraumatic stress disorder. In rodents, it has been shown to reduce anxiety in a number of behavioral paradigms including Pavlovian fear conditioning. We have recently found that expression of conditioned contextual (but not auditory) freezing in rats can be suppressed by infusion of ALLO into the bed nucleus of the stria terminalis (BNST)...
January 16, 2017: Hormones and Behavior
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