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https://www.readbyqxmd.com/read/28544095/phenotypic-assays-for-mycobacterium-tuberculosis-infection
#1
Ok-Ryul Song, Nathalie Deboosere, Vincent Delorme, Christophe J Queval, Gaspard Deloison, Elisabeth Werkmeister, Frank Lafont, Alain Baulard, Raffaella Iantomasi, Priscille Brodin
Tuberculosis (TB) is still a major global threat, killing more than one million persons each year. With the constant increase of Mycobacterium tuberculosis strains resistant to first- and second-line drugs, there is an urgent need for the development of new drugs to control the propagation of TB. Although screenings of small molecules on axenic M. tuberculosis cultures were successful for the identification of novel putative anti-TB drugs, new drugs in the development pipeline remains scarce. Host-directed therapy may represent an alternative for drug development against TB...
May 19, 2017: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
https://www.readbyqxmd.com/read/28543168/a-new-tool-to-tackle-the-opioid-epidemic-description-utility-and-results-from-the-maine-diversion-alert-program
#2
Brian J Piper, Clare E Desrosiers, Harriet C Fisher, Kenneth L McCall, Stephanie D Nichols
STUDY OBJECTIVE: The opioid epidemic continues to impact the United States, and new strategies are needed to combat this epidemic. The objective of this study was to analyze 2015 drug arrest data from Maine's Diversion Alert program (diversionalert. org), compare arrest data between the first quarters of 2015 and 2016, and provide an analysis of the sex differences in the arrests as well as information about DA use. STUDY DESIGN: A population-based, descriptive study using data from the Maine Diversion Alert Program...
May 19, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28523588/advances-in-the-development-of-janus-kinase-inhibitors-in-inflammatory-bowel-disease-future-prospects
#3
Mathurin Flamant, Josselin Rigaill, Stephane Paul, Xavier Roblin
Inflammatory bowel disease (IBD) is caused by a dysregulation of the immune system, inducing the production of proinflammatory cytokines and adhesion molecules. A better understanding of the mucosal immune response in IBD has led to the development of new drugs directed at inflammatory cytokines and leukocyte-trafficking molecules. Beyond tumor necrosis factor antagonists and anti-integrin molecules, which act by blocking the interaction between gut-specific lymphocytes and their receptor on vascular endothelium, the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway represents a new target in IBD...
May 18, 2017: Drugs
https://www.readbyqxmd.com/read/28510328/genetic-variants-in-the-genes-encoding-rho-gtpases-and-related-regulators-predict-cutaneous-melanoma-specific-survival
#4
Shun Liu, Yanru Wang, William Xue, Hongliang Liu, Yinghui Xu, Qiong Shi, Wenting Wu, Dakai Zhu, Christopher I Amos, Shenying Fang, Jeffrey E Lee, Terry Hyslop, Yi Li, Jiali Han, Qingyi Wei
Rho GTPases control cell division, motility, adhesion, vesicular trafficking and phagocytosis, which may affect progression and/or prognosis of cancers. Here, we investigated associations between genetic variants of Rho GTPases-related genes and cutaneous melanoma-specific survival (CMSS) by re-analyzing a published melanoma genome-wide association study (GWAS) and validating the results in another melanoma GWAS. In the single-locus analysis of 36,018 SNPs in 129 Rho-related genes, 427 SNPs were significantly associated with CMSS (p < 0...
May 16, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28490630/understanding-phospholipid-function-why-are-there-so-many-lipids
#5
William Dowhan
In the 1970's phospholipids were still considered mere building blocks of the membrane lipid bilayer, but the subsequent realization that phospholipids could also serve as second messengers brought new interest to the field. My own passion for the unique amphipathic properties of lipids led me to seek other, non-signaling functions for phospholipids, particularly in their interactions with membrane proteins. This seemed the last frontier in protein chemistry and enzymology to be conquered. I was fortunate to find my way to Eugene Kennedy's laboratory where both membrane proteins and phospholipids were foci of study thus providing a jumping-off point for advancing our fundamental understanding of lipid synthesis, membrane protein biosynthesis, phospholipid and membrane protein trafficking and the cellular roles of phospholipids...
May 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28475384/optimizing-pharmacologic-management-of-inflammatory-bowel-disease
#6
REVIEW
Shannon Chang, Stephen Hanauer
As our medical armamentarium for IBD continues to expand, it is essential that clinicians understand both optimizing and sequencing of individual and combination therapeutic approaches with available medications. Areas covered: This review summarizes dosing strategies and therapeutic drug monitoring for pharmacologic optimization in IBD. Aminosalicylates remain first-line therapies for mild-to-moderate UC but have limited evidence of efficacy in CD. Budesonide provides an alternative to aminosalicylates when targeted to appropriate sites in the distal small bowel and colon, as do conventional corticosteroids when applied rectally...
June 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28449273/systematic-review-the-safety-of-vedolizumab-for-the-treatment-of-inflammatory-bowel-disease
#7
REVIEW
W A Bye, V Jairath, S P L Travis
BACKGROUND: Vedolizumab specifically recognises the α4β7 integrin and selectively blocks gut lymphocyte trafficking: potentially, it offers gut-specific immunosuppression. AIM: To review the safety of vedolizumab and summarise post-marketing data to assess if any safety concerns that differ from registration trials have emerged. METHOD: A systematic bibliographic search identified six registration trials and nine cohort studies. RESULTS: Integrated data from registration trials included 2830 vedolizumab-exposed patients (4811 person-years exposure [PYs]) and 513 placebo patients...
July 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28433559/the-kcnh2-ivs9-28a-g-mutation-causes-aberrant-isoform-expression-and-herg-trafficking-defect-in-cardiomyocytes-derived-from-patients-affected-by-long-qt-syndrome-type-2
#8
Manuela Mura, Ashish Mehta, Chrishan J Ramachandra, Rita Zappatore, Federica Pisano, Maria Chiara Ciuffreda, Vincenzo Barbaccia, Lia Crotti, Peter J Schwartz, Winston Shim, Massimiliano Gnecchi
BACKGROUND: Long QT Syndrome type 2 (LQT2) is caused by mutations in the KCNH2 gene that encodes for the α-subunit (hERG) of the ion channel conducting the rapid delayed rectifier potassium current (IKr). We have previously identified a disease causing mutation (IVS9-28A/G) in the branch point of the splicing of KCNH2 intron 9. However, the mechanism through which this mutation causes the disease is unknown. METHODS AND RESULTS: We generated human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) from fibroblasts of two IVS9-28A/G mutation carriers...
April 12, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28423549/her2-specific-recombinant-immunotoxin-4d5scfv-pe40-passes-through-retrograde-trafficking-route-and-forces-cells-to-enter-apoptosis
#9
Evgeniya Sokolova, Evgeniy Guryev, Andrey Yudintsev, Vladimir Vodeneev, Sergey Deyev, Irina Balalaeva
Immunotoxin 4D5scFv-PE40 is a recombinant protein that comprises 4D5scFv antibody as a targeting module and fragment of Pseudomonas exotoxin A as an effector (toxic) one. The immunotoxin has shown pronounced antitumor effect on cancer cells overexpressing HER2 receptor in vitro and on HER2-positive experimental tumors in vivo. We clarified the mechanism of 4D5scFv-PE40 activity that is of particular importance in the case of targeted therapeutic agent aimed at personalizing treatment of disease in relation to molecular genetic characteristics of each patient...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28399084/-the-peculiarities-of-the-comprehensive-study-of-buprenorphine
#10
G K Lobacheva, E A Simonov, V Yu Kuzovlev, D V Kairgaliev, Yu V Gavrilin, Yu M Atroshchenko
The authors describe the methods of pharmaceutical and criminalistics analysis that are finding the increasingly wider application for the drug expertise (identification) and elucidation of the circumstances conducive to the commission of an offence. The special emphasis is laid on the buprenorphine studies with the use of the colour chemical reactions, thin-layer chromatography, gas chromatographic analysis, high-performance liquid chromatography, IR spectrometry, and other modern techniques. The methods based on the recent achievements in pharmaceutical and criminalistics sciences can be employed in the activities intended to control the illegal drug circulation...
2017: Sudebno-meditsinskaia Ekspertiza
https://www.readbyqxmd.com/read/28395139/next-generation-precision-polyesters-enabling-optimization-of-ligand-receptor-stoichiometry-for-modular-drug-delivery
#11
Raghu Ganugula, Meenakshi Arora, Prabhjot Saini, Melissa Guada, Majeti N V Ravi Kumar
The success of receptor-mediated drug delivery primarily depends on the ability to optimize ligand-receptor stoichiometry. Conventional polyesters such as polylactide (PLA) or its copolymer, polylactide-co-glycolide (PLGA), do not allow such optimization due to their terminal functionality. We herein report the synthesis of 12 variations of the PLA-poly(ethylene glycol) (PEG) based precision-polyester (P2s) platform, permitting 5-12 periodically spaced carboxyl functional groups on the polymer backbone. These carboxyl groups were utilized to achieve variable degrees of gambogic acid (GA) conjugation to facilitate ligand-receptor stoichiometry optimization...
April 19, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28376702/high-throughput-screening-for-readthrough-modulators-of-cftr-ptc-mutations
#12
Feng Liang, Haibo Shang, Nikole J Jordan, Eric Wong, Dayna Mercadante, Josef Saltz, Jerome Mahiou, Hermann J Bihler, Martin Mense
Cystic fibrosis (CF) is a hereditary disease caused by mutations in the gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR). A large number of nearly 2000 reported mutations, including the premature termination codon (PTC) mutations, urgently require new and personalized medicines. We have developed cell-based assays for readthrough modulators of CFTR PTC mutations (or nonsense mutation suppressors), based on the trafficking and surface expression of CFTR. Approximately 85,000 compounds have been screened for two PTC mutations (Y122X and W1282X)...
June 2017: SLAS Technology
https://www.readbyqxmd.com/read/28366874/impaired-vitreous-composition-and-retinal-pigment-epithelium-function-in-the-foxg1-lrp2-myopic-mice
#13
Olivier Cases, Antoine Obry, Sirine Ben-Yacoub, Sébastien Augustin, Antoine Joseph, Géraldine Toutirais, Manuel Simonutti, Annabel Christ, Pascal Cosette, Renata Kozyraki
High myopia (HM) is one of the main causes of visual impairment and blindness all over the world and an unsolved medical problem. Persons with HM are predisposed to other eye pathologies such as retinal detachment, myopic retinopathy or glaucomatous optic neuropathy, complications that may at least partly result from the extensive liquefaction of the myopic vitreous gel. To identify the involvement of the liquid vitreous in the pathogenesis of HM we here analyzed the vitreous of the recently described highly myopic low density lipoprotein receptor-related protein 2 (Lrp2)-deficient eyes...
March 31, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28239348/genetic-determinants-of-parkinson-s-disease-can-they-help-to-stratify-the-patients-based-on-the-underlying-molecular-defect
#14
REVIEW
Sara Redenšek, Maja Trošt, Vita Dolžan
Parkinson's disease (PD) is a sporadic progressive neurodegenerative brain disorder with a relatively strong genetic background. We have reviewed the current literature about the genetic factors that could be indicative of pathophysiological pathways of PD and their applications in everyday clinical practice. Information on novel risk genes is coming from several genome-wide association studies (GWASs) and their meta-analyses. GWASs that have been performed so far enabled the identification of 24 loci as PD risk factors...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28238355/prevalence-contexts-and-correlates-of-child-sexual-abuse-in-cyprus
#15
Eleni Karayianni, Kostas A Fanti, Irene-Anna Diakidoy, Maria-Zoe Hadjicharalambous, Evita Katsimicha
It is well documented that child sexual abuse (CSA) may be one of the major public health problems in the world, especially due to the co-occurrence with other types of abuse and negative developmental outcomes. The aim of the current study was the comprehensive examination of CSA with respect to its prevalence, its contexts of occurrence and its correlates. The sample included 1852 adolescents and young adults (15-25 years old; 441 males), recruited through schools, universities and other youth organizations across Cyprus...
February 18, 2017: Child Abuse & Neglect
https://www.readbyqxmd.com/read/28237838/gene-therapeutic-reversal-of-peripheral-olfactory-impairment-in-bardet-biedl-syndrome
#16
Corey L Williams, Cedric R Uytingco, Warren W Green, Jeremy C McIntyre, Kirill Ukhanov, Arthur D Zimmerman, Dana T Shively, Lian Zhang, Darryl Y Nishimura, Val C Sheffield, Jeffrey R Martens
Olfactory dysfunction is a pervasive but underappreciated health concern that affects personal safety and quality of life. Patients with olfactory dysfunctions have limited therapeutic options, particularly those involving congenital diseases. Bardet-Biedl syndrome (BBS) is one such disorder, where olfactory loss and other symptoms manifest from defective cilium morphology and/or function in various cell types/tissues. Olfactory sensory neurons (OSNs) of BBS mutant mice lack the capacity to build/maintain cilia, rendering the cells incapable of odor detection...
April 5, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28141609/identification-and-management-of-human-trafficking-victims-in-the-emergency-department
#17
REVIEW
Lisa M Hachey, Julia C Phillippi
Health care practitioners serve an important role in identification and assistance of human trafficking victims. Advanced practice registered nurses, including certified nurse midwives, clinical nurse specialists, and nurse practitioners, are in a unique position to interact with persons trafficked and seen in the clinical setting, yet they require knowledge to identify the signs of human trafficking. Lack of training and education has been identified as a barrier for health care professionals to recognize human trafficking victims and implement needed health care services (; )...
January 2017: Advanced Emergency Nursing Journal
https://www.readbyqxmd.com/read/28107158/human-trafficking-in-areas-of-conflict-health-care-professionals-duty-to-act
#18
Christina Bloem, Rikki E Morris, Makini Chisolm-Straker
Given the significant global burden of human trafficking, the ability of clinicians to identify and provide treatment for trafficked persons is critical. Particularly in conflict settings, health care facilities often serve as the first and sometimes only point of contact for trafficked persons. As such, medical practitioners have a unique opportunity and an ethical imperative to intervene, even in nonclinical roles. With proper training, medical practitioners can assist trafficked persons by documenting human trafficking cases, thereby placing pressure on key stakeholders to enforce legal protections, and by providing adequate services to those trafficked...
January 1, 2017: AMA Journal of Ethics
https://www.readbyqxmd.com/read/28107156/mandatory-reporting-of-human-trafficking-potential-benefits-and-risks-of-harm
#19
Abigail English
Human trafficking, including both sex and labor trafficking, has profound consequences for the safety, health, and well-being of victims and survivors. Efforts to address human trafficking through prevention, protection, and prosecution are growing but remain insufficient. Mandatory reporting has the potential to bring victims and survivors to the attention of social service and law enforcement agencies but may discourage trafficked persons from seeking help, thereby limiting the ability of health care professionals to establish trust and provide needed care...
January 1, 2017: AMA Journal of Ethics
https://www.readbyqxmd.com/read/28027812/new-psychoactive-substances-nps-on-cryptomarket-fora-an-exploratory-study-of-characteristics-of-forum-activity-between-nps-buyers-and-vendors
#20
Marie Claire Van Hout, Evelyn Hearne
BACKGROUND: The continual diversification of new psychoactive substances (NPS) circumventing legislation creates a public health and law enforcement challenge, and one particularly challenged by availability on Hidden Web cryptomarkets. METHODS: This is the first study of its kind which aimed to explore and characterise cryptomarket forum members' views and perspectives on NPS vendors and products within the context of Hidden Web community dynamics. An internal site search was conducted on two cryptomarkets popular with NPS vendors and hosting fora; Alphabay and Valhalla, using the search terms of 40 popular NPS in the seven categories of stimulant/cathinone; GABA activating; hallucinogen, dissociative, cannabinoid, opioid and other/unspecified/uncategorised NPS...
December 24, 2016: International Journal on Drug Policy
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