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https://www.readbyqxmd.com/read/29740351/pain-therapy-guided-by-purpose-and-perspective-in-light-of-the-opioid-epidemic
#1
REVIEW
Amie L Severino, Arash Shadfar, Joshua K Hakimian, Oliver Crane, Ganeev Singh, Keith Heinzerling, Wendy M Walwyn
Prescription opioid misuse is an ongoing and escalating epidemic. Although these pharmacological agents are highly effective analgesics prescribed for different types of pain, opioids also induce euphoria, leading to increasing diversion and misuse. Opioid use and related mortalities have developed in spite of initial claims that OxyContin, one of the first opioids prescribed in the USA, was not addictive in the presence of pain. These claims allayed the fears of clinicians and contributed to an increase in the number of prescriptions, quantity of drugs manufactured, and the unforeseen diversion of these drugs for non-medical uses...
2018: Frontiers in Psychiatry
https://www.readbyqxmd.com/read/29727811/development-and-psychometric-evaluation-of-the-pornography-purchase-task
#2
Kyler Mulhauser, Emily Miller Short, Jeremiah Weinstock
Excessive pornography use and hypersexuality are frequently evaluated via direct self-report of problem severity and negative consequences associated with these behaviors. These face-valid assessments may be less sensitive to problems of hypersexuality in persons with low insight into their condition or in persons with motivation to minimize the negative impact of their pornography use. Demand for addictive substances has been effectively evaluated through a behavioral economic framework using a hypothetical purchase task, in which respondents are asked to report their degree of engagement with the substance as the financial costs associated with use increase...
April 26, 2018: Addictive Behaviors
https://www.readbyqxmd.com/read/29705685/translational-genomics-in-pancreatic-ductal-adenocarcinoma-a-review-with-re-analysis-of-tcga-dataset
#3
REVIEW
Jeffery Ho, Xianchun Li, Lin Zhang, Yonghao Liang, Wei Hu, Johnny C W Yau, Hung Chan, Tony Gin, Matthew T V Chan, Gary Tse, William K K Wu
Malignancy of the pancreas is a leading cause of cancer-related mortality, with the highest case-fatality of all cancers. Nevertheless, the lack of sensitive biomarkers and presence of biological heterogeneity precludes its early detection and effective treatment. The recent introduction of next-generation sequencing allows characterization of multiple driver mutations at genome- and exome-wide levels. Sequencing of DNA and RNA from circulating tumour cells has also opened an exciting era of non-invasive procedures for tumour detection and prognostication...
April 25, 2018: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29703765/role-of-epidermal-growth-factor-receptor-egfr-inhibitors-and-radiation-in-the-management-of-brain-metastases-from-egfr-mutant-lung-cancers
#4
REVIEW
Melin J Khandekar, Zofia Piotrowska, Henning Willers, Lecia V Sequist
The growth of genotype-directed targeted therapies, such as inhibitors of the epidermal growth factor receptor (EGFR), has revolutionized treatment for some patients with oncogene-addicted lung cancer. However, as systemic control for these patients has improved, brain metastases remain an important source of morbidity and mortality. Traditional treatment for brain metastases has been radiotherapy, either whole-brain radiation or stereotactic radiosurgery. The growing availability of drugs that can cross the blood-brain barrier and have activity in the central nervous system (CNS) has led to many studies investigating whether targeted therapy can be used in combination with or in lieu of radiation...
April 27, 2018: Oncologist
https://www.readbyqxmd.com/read/29681866/study-protocol-using-deep-brain-stimulation-multimodal-neuroimaging-and-neuroethics-to-understand-and-treat-severe-enduring-anorexia-nervosa
#5
Rebecca J Park, Jessica C Scaife, Tipu Z Aziz
Background: Research suggests that altered eating and the pursuit of thinness in anorexia nervosa (AN) are, in part, a consequence of aberrant reward circuitry. The neural circuits involved in reward processing and compulsivity overlap significantly, and this has been suggested as a transdiagnostic factor underpinning obsessive compulsive disorder, addictions and eating disorders. The nucleus accumbens (NAcc) is central to both reward processing and compulsivity. In previous studies, deep-brain stimulation (DBS) to the NAcc has been shown to result in neural and symptomatic improvement in both obsessive compulsive disorder and addictions...
2018: Frontiers in Psychiatry
https://www.readbyqxmd.com/read/29680318/using-a-randomized-controlled-trial-to-test-whether-modifications-to-contingency-management-improve-outcomes-for-heavy-drinkers-with-serious-mental-illness
#6
Oladunni Oluwoye, Jordan Skalisky, Ekaterina Burduli, Naomi S Chaytor, Sterling McPherson, Sean Murphy, Jalene Herron, Katherine Hirchak, Mason Burley, Richard K Ries, John M Roll, Michael G McDonell
BACKGROUND: In contingency management (CM), individuals receive rewards for alcohol abstinence. CM is associated with reduced alcohol use in adults with co-occurring serious mental illnesses (SMI). Pre-treatment urine ethyl glucuronide (uEtG) levels equivalent to daily heavy drinking (uEtG > 349 ng/mL) are associated with poor response to CM. Modifications to CM are needed to improve outcomes for non-responders. AIMS: To determine if pre-treatment heavy drinkers, defined by uEtG, with SMI achieve higher levels of alcohol abstinence when they receive an increased magnitude of reinforcement for abstinence (High-Magnitude CM) or reinforcers for reduced drinking, prior to receiving reinforcers for abstinence (Shaping CM), relative to those who receive typical low-magnitude abstinence based CM (Usual CM)...
April 19, 2018: Contemporary Clinical Trials
https://www.readbyqxmd.com/read/29680151/vmat2-inhibitors-and-the-path-to-ingrezza-valbenazine
#7
Nicole D Harriott, John P Williams, Evan B Smith, Haig P Bozigian, Dimitri E Grigoriadis
The dopaminergic system plays a key role in the central nervous system, regulating executive function, arousal, reward, and motor control. Dysregulation of this critical monoaminergic system has been associated with diseases of the central nervous system including schizophrenia, Parkinson's disease, and disorders such as attention deficit hyperactivity disorders and addiction. Drugs that modify the dopaminergic system by modulating the activity of dopamine have been successful in demonstrating clinical efficacy by providing treatments for these diseases...
2018: Progress in Medicinal Chemistry
https://www.readbyqxmd.com/read/29669731/involvement-of-activated-brain-stress-responsive-systems-in-excessive-and-relapse-alcohol-drinking-in-rodent-models-implications-for-therapeutics
#8
Yan Zhou, Mary Jeanne Kreek
Addictive diseases, including addiction to alcohol pose massive public health costs. Addiction is a chronic relapsing disease, caused by both the direct effects induced by drugs and persistent neuroadaptations at several (molecular, cellular and behavioral) levels. These drug-type specific neuro-adaptations are brought on largely by the reinforcing effects of drugs on the central nervous system and environment, including stress. Results from animal experiments have demonstrated important interactions between alcohol and the stress responsive systems...
April 18, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29651507/efficacy-and-side-effects-of-baclofen-and-the-novel-gaba-b-receptor-positive-allosteric-modulator-cmppe-in-animal-models-for-alcohol-and-cocaine-addiction
#9
Valentina Vengeliene, Tatiane T Takahashi, Olga A Dravolina, Irina Belozertseva, Edwin Zvartau, Anton Y Bespalov, Rainer Spanagel
RATIONALE: Preclinical studies suggest that the GABAB receptor is a potential target for treatment of substance use disorders. However, recent clinical trials report adverse effects in patients treated with the GABAB receptor agonist baclofen and even question efficacy. How can the discrepancy between preclinical and clinical findings be explained? OBJECTIVE: To test efficacy and adverse effects of baclofen and the novel GABAB positive allosteric modulator (PAM) CMPPE in rat addiction models, which were developed in accordance with DSM...
April 12, 2018: Psychopharmacology
https://www.readbyqxmd.com/read/29643474/histone-deacetylase-6-controls-notch3-trafficking-and-degradation-in-t-cell-acute-lymphoblastic-leukemia-cells
#10
Marica Pinazza, Margherita Ghisi, Sonia Minuzzo, Valentina Agnusdei, Gianluca Fossati, Vincenzo Ciminale, Laura Pezzè, Yari Ciribilli, Giorgia Pilotto, Carolina Venturoli, Alberto Amadori, Stefano Indraccolo
Several studies have revealed that endosomal sorting controls the steady-state levels of Notch at the cell surface in normal cells and prevents its inappropriate activation in the absence of ligands. However, whether this highly dynamic physiologic process can be exploited to counteract dysregulated Notch signaling in cancer cells remains unknown. T-ALL is a malignancy characterized by aberrant Notch signaling, sustained by activating mutations in Notch1 as well as overexpression of Notch3, a Notch paralog physiologically subjected to lysosome-dependent degradation in human cancer cells...
April 12, 2018: Oncogene
https://www.readbyqxmd.com/read/29627310/understanding-antidepressant-discontinuation-syndrome-ads-through-preclinical-experimental-models
#11
REVIEW
Konstantin N Zabegalov, Tatiana O Kolesnikova, Sergey L Khatsko, Andrey D Volgin, Oleg A Yakovlev, Tamara G Amstislavskaya, Polina A Alekseeva, Darya A Meshalkina, Ashton J Friend, Wandong Bao, Konstantin A Demin, Raul R Gainetdinov, Allan V Kalueff
Antidepressant drugs are currently one of the most prescribed medications. In addition to treatment resistance and side effects of antidepressants, their clinical use is further complicated by antidepressant discontinuation syndrome (ADS). ADS is a common problem in patients following the interruption, dose reduction, or discontinuation of antidepressant drugs. Clinically, ADS resembles a classical drug withdrawal syndrome, albeit differing from it because antidepressants generally do not induce addiction. The growing clinical importance and prevalence of ADS necessitate novel experimental (animal) models of this disorder...
April 5, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29580163/from-homer-and-hippocrates-to-modern-personalized-medicine-is-there-a-role-for-pharmacoepigenomics-in-the-treatment-of-alcohol-addiction
#12
Georgia Ragia, Vangelis G Manolopoulos
From the earliest times to the present, alcohol has evolved as part of life and culture. For most adults, moderate alcohol use is harmless, however, it lies at one end of a range that moves through alcohol abuse to alcohol addiction. Alcohol addiction is a serious and chronic psychiatric disorder that, on top of its heavy consequences on health, also brings significant social and economic losses to individuals and society at large. Pharmacotherapy of alcohol addiction exists, but its effectiveness varies significantly among individuals...
March 27, 2018: Pharmacogenomics
https://www.readbyqxmd.com/read/29578946/the-bivalent-ligand-mcc22-potently-attenuates-nociception-in-a-murine-model-of-sickle-cell-disease
#13
Giuseppe Cataldo, Mary M Lunzer, Julie K Olson, Eyup Akgün, John D Belcher, Gregory M Vercellotti, Philip S Portoghese, Donald A Simone
Sickle cell disease (SCD) is a chronic inflammatory disorder accompanied by chronic pain. In addition to ongoing pain and hyperalgesia, vaso-occlusive crises-induced pain can be chronic or episodic. Since analgesics typically used to treat pain are not very effective in SCD, opioids, including morphine, are a primary treatment for managing pain in SCD but are associated with many serious side effects, including constipation, tolerance, addiction, and respiratory depression. Thus, there is a need for the development of novel treatments for pain in SCD...
March 22, 2018: Pain
https://www.readbyqxmd.com/read/29569991/examining-perceived-stress-childhood-trauma-and-interpersonal-trauma-in-individuals-with-drug-addiction
#14
Julia Garami, Ahmad Valikhani, Denise Parkes, Paul Haber, Justin Mahlberg, Blazej Misiak, Dorota Frydecka, Ahmed A Moustafa
The investigation of psychosocial factors in relation to opiate addiction is limited and typically uses binary measures to assess how incidences of childhood trauma correlate with addiction. There has also been a lack of enquiry into how experiences of noninterpersonal versus interpersonal trauma may impact drug use addiction. In this regard, the current study utilized a novel measurement of interpersonal versus noninterpersonal lifetime trauma and a scale assessing severity of childhood trauma to examine how these factors may impact patients with opioid addiction...
January 1, 2018: Psychological Reports
https://www.readbyqxmd.com/read/29561290/pilot-investigation-randomized-controlled-analog-trial-for-alcohol-and-tobacco-smoking-co-addiction-using-contingency-management
#15
Michael F Orr, Crystal Lederhos Smith, Myles Finlay, Samantha C Martin, Olivia Brooks, Oladunni A Oluwoye, Emily Leickly, Michael McDonell, Ekaterina Burduli, Celestina Barbosa-Leiker, Matt Layton, John M Roll, Sterling M McPherson
Contingency management (CM) is associated with decreases in off-target drug and alcohol use during primary target treatment. The primary hypothesis for this trial was that targeting alcohol use or tobacco smoking would yield increased abstinence in the opposite, nontargeted drug. We used a 2 [CM vs. noncontingent control (NC) for alcohol]×2 (CM vs. NC for smoking tobacco) factorial design, with alcohol intake (through urinary ethyl glucuronide) and tobacco smoking (through urinary cotinine) as the primary outcomes...
March 20, 2018: Behavioural Pharmacology
https://www.readbyqxmd.com/read/29541451/cancer-cell-metabolic-plasticity-allows-resistance-to-nampt-inhibition-but-invariably-induces-dependence-on-ldha
#16
Natthakan Thongon, Chiara Zucal, Vito Giuseppe D'Agostino, Toma Tebaldi, Silvia Ravera, Federica Zamporlini, Francesco Piacente, Ruxanda Moschoi, Nadia Raffaelli, Alessandro Quattrone, Alessio Nencioni, Jean-Francois Peyron, Alessandro Provenzani
Background: Inhibitors of nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in NAD+ biosynthesis from nicotinamide, exhibit anticancer effects in preclinical models. However, continuous exposure to NAMPT inhibitors, such as FK866, can induce acquired resistance. Methods: We developed FK866-resistant CCRF-CEM (T cell acute lymphoblastic leukemia) and MDA MB231 (breast cancer) models, and by exploiting an integrated approach based on genetic, biochemical, and genome wide analyses, we annotated the drug resistance mechanisms...
2018: Cancer & Metabolism
https://www.readbyqxmd.com/read/29535424/comprehensive-genomic-profiling-of-neuroendocrine-bladder-cancer-pinpoints-molecular-origin-and-potential-therapeutics
#17
Peiye Shen, Ying Jing, Ruiyun Zhang, Mei-Chun Cai, Pengfei Ma, Haige Chen, Guanglei Zhuang
Neuroendocrine bladder cancer is a relatively rare but often lethal malignancy, with cell of origin, oncogenomic architecture and standard treatment poorly defined. Here we performed comprehensive whole-genome and transcriptome sequencing on a unique cohort of genitourinary neuroendocrine neoplasms, mainly small cell carcinomas of the urinary bladder. The mutational landscape and signatures of neuroendocrine bladder cancer strikingly resembled those in conventional urothelial carcinoma, along with typically mixed histologies, supporting a common cellular origin...
March 14, 2018: Oncogene
https://www.readbyqxmd.com/read/29520592/decrease-of-cocaine-but-not-heroin-self-administration-and-relapse-by-the-tyrosine-kinase-inhibitor-masitinib-in-male-sprague-dawley-rats
#18
A Belin-Rauscent, J Lacoste, O Hermine, A Moussy, B J Everitt, David Belin
RATIONALE: Accumulating evidence shows that cocaine, and also heroin, influence several tyrosine kinases, expressed in neurons and in non-neuronal populations such as microglia, astrocytes and mast-cells. Drug-induced activation of mast cells both triggers inflammatory processes in the brain mediated by the glial cells they activate, and facilitates histamine release which may directly influence the dopamine system. Thus, by triggering the activation and degranulation of mast cells dependent on the tyrosine kinase c-kit and Fyn, the latter being also involved in NMDA-dependent synaptic plasticity, cocaine and heroin may indirectly influence the neural mechanisms that mediate their reinforcing properties...
May 2018: Psychopharmacology
https://www.readbyqxmd.com/read/29514413/heroin-seeking-becomes-dependent-on-dorsal-striatal-dopaminergic-mechanisms-and-can-be-decreased-by-n-acetylcysteine
#19
Ritchy Hodebourg, Jennifer E Murray, Maxime Fouyssac, Mickaël Puaud, Barry J Everitt, David Belin
The alarming increase in heroin overdoses in the USA is a reminder of the need for efficacious and novel treatments for opiate addiction. This may reflect the relatively poor understanding of the neural basis of heroin, as compared to cocaine, seeking behaviour. While cocaine reinforcement depends on the mesolimbic system, well-established cocaine seeking is dependent on dorsolateral striatum (aDLS) dopamine-dependent mechanisms which are disrupted by N-acetylcysteine, through normalisation of corticostriatal glutamate homeostasis...
March 7, 2018: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29502754/treatment-considerations-in-internet-and-video-game-addiction-a-qualitative-discussion
#20
REVIEW
David N Greenfield
Internet and video game addiction has been a steadily developing consequence of modern living. Behavioral and process addictions and particularly Internet and video game addiction require specialized treatment protocols and techniques. Recent advances in addiction medicine have improved our understanding of the neurobiology of substance and behavioral addictions. Novel research has expanded the ways we understand and apply well-established addiction treatments as well as newer therapies specific to Internet and video game addiction...
April 2018: Child and Adolescent Psychiatric Clinics of North America
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