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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
#1
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/29156647/effects-of-nutritional-interventions-during-pregnancy-on-infant-and-child-cognitive-outcomes-a-systematic-review-and-meta-analysis
#2
REVIEW
Rachael M Taylor, Shanna M Fealy, Alessandra Bisquera, Roger Smith, Clare E Collins, Tiffany-Jane Evans, Alexis J Hure
BACKGROUND: Epidemiological studies have demonstrated that folate, iodine and iron intake during pregnancy impacts on foetal brain development and cognitive function. However, in human studies, the relationship with other dietary nutrients is less clear. OBJECTIVE: This systematic review aims to critically appraise the current literature and meta-analyses results from nutritional interventions during pregnancy that aimed to optimise infant and child cognitive outcomes...
November 20, 2017: Nutrients
https://www.readbyqxmd.com/read/29156557/the-invasive-region-of-glioblastoma-defined-by-5ala-guided-surgery-has-an-altered-cancer-stem-cell-marker-profile-compared-to-central-tumour
#3
Stuart J Smith, Mohammed Diksin, Saachi Chhaya, Shwetha Sairam, Maria A Estevez-Cebrero, Ruman Rahman
Glioblastoma, a WHO grade IV astrocytoma, is a highly aggressive and heterogeneous tumour that infiltrates deeply into surrounding brain parenchyma, making complete surgical resection impossible. Despite chemo-radiotherapy, the residual cell population within brain parenchyma post-surgery causes inevitable recurrence. Previously, the tumour core has been the focus of research and the basis for targeted therapeutic regimes, which have failed to improve survival in clinical trials. Here, we focus on the invasive margin as defined by the region with 5-aminolevulinic acid (5ALA) (GliolanTM) fluorescence at surgery beyond the T1 enhancing region on magnetic resonance imaging (MRI)...
November 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29156279/the-stocks-and-flows-of-nitrogen-phosphorus-and-potassium-across-a-30-year-time-series-for-agriculture-in-huantai-county-china
#4
Jessica Bellarby, Ben W J Surridge, Philip M Haygarth, Kun Liu, Giuseppina Siciliano, Laurence Smith, Clive Rahn, Fanqiao Meng
In order to improve the efficiency of nutrient use whilst also meeting projected changes in the demand for food within China, new nutrient management frameworks comprised of policy, practice and the means of delivering change are required. These frameworks should be underpinned by systemic analyses of the stocks and flows of nutrients within agricultural production. In this paper, a 30-year time series of the stocks and flows of nitrogen (N), phosphorus (P) and potassium (K) are reported for Huantai county, an exemplar area of intensive agricultural production in the North China Plain...
November 17, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/29156212/history-and-purpose-of-postpartum-support-international
#5
Wendy Newhouse Davis, Christena Raines, Pec Indman, Birdie Gunyon Meyer, Ann Smith
Postpartum Support International provides training for professionals and supports families who experience perinatal mood and anxiety disorders. The purpose of this article is to describe Postpartum Support International, which was founded in 1987 to increase awareness among public and professional communities about the emotional difficulties women experience during and after pregnancy. We recommend strategies with which health care professionals can support families, reduce stigma, and offer resources for treatment and support...
November 17, 2017: Journal of Obstetric, Gynecologic, and Neonatal Nursing: JOGNN
https://www.readbyqxmd.com/read/29156165/understanding-frontal-plane-correction-in-hallux-valgus-repair
#6
REVIEW
W Bret Smith, Paul Dayton, Robert D Santrock, Daniel J Hatch
Hallux-abducto-valgus or "bunion" surgery is one of the most common surgical procedures for the foot and ankle specialist. As our understanding of the hallux-abducto-valgus deformity has grown, it is becoming clear that the anatomic CORA of the deformity may lie at the tarsometatarsal joint. There is also the component of the 3-dimensional nature of the deformity that may be best addressed at this CORA. With these issues in mind, it was necessary to address the shortcomings of the traditional Lapidus procedure and progress toward more consistent, instrumented steps that could address the 3-dimensional nature of the deformity...
January 2018: Clinics in Podiatric Medicine and Surgery
https://www.readbyqxmd.com/read/29155981/des-acyl-ghrelin-decreases-anxiety-like-behavior-in-male-mice
#7
Parinaz Mahbod, Eric P Smith, Maureen E Fitzgerald, Rachel L Morano, Benjamin A Packard, Sriparna Ghosal, Jessie R Scheimann, Diego Perez-Tilve, James P Herman, Jenny Tong
Ghrelin is a 28-amino acid polypeptide that regulates feeding, glucose metabolism and emotionality (stress, anxiety and depression). Plasma ghrelin circulates as desacyl ghrelin (DAG) or in an acylated form, acyl ghrelin (AG), through the actions of Ghrelin -O-Acyltransferase (GOAT), exhibiting low or high affinity, respectively, for the growth hormone secretagogue receptor (GHSR1a). We investigated the role of endogenous AG, DAG and GHSR1a signaling on anxiety and stress responses using ghrelin knockout (Ghr KO), GOAT KO, and Ghsr-stop-floxed (Ghsr null) mice...
November 15, 2017: Endocrinology
https://www.readbyqxmd.com/read/29155958/effect-of-preoperative-opioid-dosage-on-postoperative-period-after-thoracic-spinal-cord-stimulator-surgery
#8
Ravichandra A Madineni, Colin M Smith, Shannon W Clark, David W Boorman, Chengyuan Wu, Dajie Wang, James S Harrop, Ashwini D Sharan
Objective: We aim to study the impact of preoperative opioid dosage on postoperative length of stay (LOS) in patients undergoing thoracic spinal cord stimulator (SCS) placement surgery as a primary objective. Secondary objectives of this study include investigating patient-controlled analgesia (PCA) usage and postoperative complications like fever in relation to patients' preoperative opioid dosage and postoperative LOS. Methods: A total of 47 patients who underwent thoracic SCS for first time were retrospectively studied through chart review...
November 16, 2017: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
https://www.readbyqxmd.com/read/29155953/max-mutations-in-endometrial-cancer-clinicopathologic-associations-and-recurrent-max-p-his28arg-functional-characterization
#9
Christopher J Walker, Craig M Rush, Paola Dama, Matthew J O'Hern, Casey M Cosgrove, Jessica L Gillespie, Roman A Zingarelli, Blair Smith, Maggie E Stein, David G Mutch, Reena Shakya, Chia-Wen Chang, Karuppaiyah Selvendiran, Jonathan W Song, David E Cohn, Paul J Goodfellow
Background: Genomic studies have revealed that multiple genes are mutated at varying frequency in endometrial cancer (EC); however, the relevance of many of these mutations is poorly understood. An EC-specific recurrent mutation in the MAX transcription factor p.His28Arg was recently discovered. We sought to assess the functional consequences of this hotspot mutation and determine its association with cancer-relevant phenotypes. Methods: MAX was sequenced in 509 endometrioid ECs, and associations between mutation status and clinicopathologic features were assessed...
November 15, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29155870/a-modified-delphi-study-to-determine-the-level-of-consensus-across-the-european-union-on-the-structures-processes-and-desired-outcomes-of-the-management-of-polypharmacy-in-older-people
#10
Derek Stewart, Kathrine Gibson-Smith, Katie MacLure, Alpana Mair, Albert Alonso, Carles Codina, Antonio Cittadini, Fernando Fernandez-Llimos, Glenda Fleming, Dimitra Gennimata, Ulrika Gillespie, Cathy Harrison, Ulrike Junius-Walker, Przemysław Kardas, Thomas Kempen, Moira Kinnear, Pawel Lewek, Joao Malva, Jennifer McIntosh, Claire Scullin, Birgitt Wiese
BACKGROUND: Inappropriate use of multiple medicines (inappropriate polypharmacy) is a major challenge in older people with consequences of increased prevalence and severity of adverse drug reactions and interactions, and reduced medicines adherence. The aim of this study was to determine the levels of consensus amongst key stakeholders in the European Union (EU) in relation to aspects of the management of polypharmacy in older people. METHODS: Forty-six statements were developed on aspects of healthcare structures, processes and desired outcomes, with consensus defined at ≥ 80% agreement...
2017: PloS One
https://www.readbyqxmd.com/read/29155770/determination-of-thermodynamic-properties-of-alkaline-earth-liquid-metal-alloys-using-the-electromotive-force-technique
#11
Thomas P Nigl, Nathan D Smith, Timothy Lichtenstein, Jarrod Gesualdi, Kuldeep Kumar, Hojong Kim
A novel electrochemical cell based on a CaF2 solid-state electrolyte has been developed to measure the electromotive force (emf) of binary alkaline earth-liquid metal alloys as functions of both composition and temperature in order to acquire thermodynamic data. The cell consists of a chemically stable solid-state CaF2-AF2 electrolyte (where A is the alkaline-earth element such as Ca, Sr, or Ba), with binary A-B alloy (where B is the liquid metal such as Bi or Sb) working electrodes, and a pure A metal reference electrode...
November 3, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29155710/dna-nanotubes-as-a-versatile-tool-to-study-semiflexible-polymers
#12
Jörg Schnauß, Martin Glaser, Jessica S Lorenz, Carsten Schuldt, Christin Möser, Martin Sajfutdinow, Tina Händler, Josef A Käs, David M Smith
Mechanical properties of complex, polymer-based soft matter, such as cells or biopolymer networks, can be understood in neither the classical frame of flexible polymers nor of rigid rods. Underlying filaments remain outstretched due to their non-vanishing backbone stiffness, which is quantified via the persistence length (lp), but they are also subject to strong thermal fluctuations. Their finite bending stiffness leads to unique, non-trivial collective mechanics of bulk networks, enabling the formation of stable scaffolds at low volume fractions while providing large mesh sizes...
October 25, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29155667/use-of-a-diagonal-approach-to-health-system-strengthening-and-measles-elimination-after-a-large-nationwide-outbreak-in-mongolia
#13
José E Hagan, Ashley Greiner, Ulzii-Orshikh Luvsansharav, Jason Lake, Christopher Lee, Roberta Pastore, Yoshihiro Takashima, Amarzaya Sarankhuu, Sodbayar Demberelsuren, Rachel Smith, Benjamin Park, James L Goodson
Measles is a highly transmissible infectious disease that causes serious illness and death worldwide. Efforts to eliminate measles through achieving high immunization coverage, well-performing surveillance systems, and rapid and effective outbreak response mechanisms while strategically engaging and strengthening health systems have been termed a diagonal approach. In March 2015, a large nationwide measles epidemic occurred in Mongolia, 1 year after verification of measles elimination in this country. A multidisciplinary team conducted an outbreak investigation that included a broad health system assessment, organized around the Global Health Security Agenda framework of Prevent-Detect-Respond, to provide recommendations for evidence-based interventions to interrupt the epidemic and strengthen the overall health system to prevent future outbreaks of measles and other epidemic-prone infectious threats...
December 2017: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/29155593/dynamical-density-functional-theory-for-the-evaporation-of-droplets-of-nanoparticle-suspension
#14
Christopher Chalmers, Roger Smith, Andrew J Archer
We develop a lattice gas model for the drying of droplets of a nanoparticle suspension on a planar surface, using dynamical density functional theory (DDFT) to describe the time evolution of the solvent and nanoparticle density profiles. The DDFT assumes a diffusive dynamics but does not include the advective hydrodynamics of the solvent, so the model is relevant to highly viscous or near to equilibrium systems. Nonetheless, we see an equivalent of the coffee-ring stain effect, but in the present model it occurs for thermodynamic rather the fluid-mechanical reasons...
November 20, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/29155338/financial-toxicity-in-bladder-cancer-patients-reasons-for-delay-in-care-and-effect-on-quality-of-life
#15
Marianne M Casilla-Lennon, Seul Ki Choi, Allison M Deal, Jeannette T Bensen, Gopal Narang, Pauline Filippou, Benjamin McCormick, Raj Pruthi, Eric Wallen, Hung-Jui Tan, Michael Woods, Matthew Nielsen, Angela Smith
PURPOSE: Costly surveillance and treatment of bladder cancer can lead to financial toxicity (FT), a treatment-related financial burden. Our objective was to define the prevalence of FT among bladder cancer patients and identify delays in care and its effect on health-related quality of life (HRQOL). METHODS: We identified bladder cancer patients in the UNC Health Registry/Cancer Survivorship Cohort. FT was defined as agreement with having "to pay more for medical care than you can afford...
November 16, 2017: Journal of Urology
https://www.readbyqxmd.com/read/29155232/refusal-of-cervical-spine-immobilization-after-blunt-trauma-implications-for-initial-evaluation-and-management-a-retrospective-cohort-study
#16
James M Tatum, Navpreet K Dhillon, Ara Ko, Eric J T Smith, Nicolas Melo, Galinos Barmparas, Eric J Ley
INTRODUCTION: Rigid cervical collars are routinely placed in the pre-hospital setting after significant blunt trauma. Patients who are deemed competent by field personnel (Glasgow Coma Scale (GCS) ≥13, no major distracting injury and not grossly intoxicated) may refuse cervical collar placement. MATERIAL AND METHODS: A retrospective review was conducted of all adult trauma patients presenting to a Level 1 trauma center after blunt trauma with a GCS≥13 and no distracting injury or gross intoxication from January 2014 to December 2014...
November 15, 2017: International Journal of Surgery
https://www.readbyqxmd.com/read/29155208/inflammatory-renin-angiotensin-system-disruption-attenuates-sensory-hyperinnervation-and-mechanical-hypersensitivity-in-a-rat-model-of-provoked-vestibulodynia
#17
Anuradha Chakrabarty, Zhaohui Liao, Ying Mu, Peter G Smith
Vestibulodynia is characterized by peri-vaginal mechanical hypersensitivity, hyperinnervation, and abundant inflammatory cells expressing renin-angiotensin system proteins. We developed a tractable rat model of vestibulodynia to further assess the contributions of the renin-angiotensin system. Complete Freund's adjuvant (CFA) injected into the posterior vestibule induced marked vestibular hypersensitivity throughout a 7-day test period. Numbers of axons immunoreactive for PGP9.5, calcitonin gene-related peptide, and GFRα2 were increased...
November 15, 2017: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/29155116/the-effect-of-steroids-on-complications-readmission-and-reoperation-after-posterior-lumbar-fusion
#18
Michael B Cloney, Roxanna M Garcia, Zachary A Smith, Nader S Dahdaleh
BACKGROUND DATA: The effects of chronic corticosteroid therapy on complications, readmission, and reoperation after posterior lumbar fusion (PLF) remains under-investigated and was examined to determine differences in outcomes. METHODS: We analyzed patients from 2006 to 2013 using the National Surgery Quality Improvement Program database (NSQIP) undergoing PLF. Patients taking steroids for a chronic condition were compared to those not taking steroids. Multivariable regression identified factors independently associated with complications, readmission, and reoperation...
November 15, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/29155045/independent-and-interactive-associations-of-negative-affect-restraint-and-impulsivity-in-relation-to-binge-eating-among-women
#19
Tyler B Mason, Kathryn E Smith, Jason M Lavender, Robin J Lewis
There is growing recognition that impulsivity may serve as an underlying risk factor for binge eating. In addition, the association of impulsivity with binge eating may be moderated by other affective and cognitive risk factors. This study examined independent and interactive associations of negative affect, dietary restraint, and facets of impulsivity with binge eating. A diverse sample of 566 undergraduate women completed online questionnaires of study variables. Results revealed a three-way interaction of negative affect, dietary restraint, and attentional impulsivity in relation to binge eating...
November 15, 2017: Appetite
https://www.readbyqxmd.com/read/29155038/a-novel-modernized-golgi-cox-stain-optimized-for-clarity-cleared-tissue
#20
Mustafa S Kassem, Sandra Y Y Fok, Kristie L Smith, Michael Kuligowski, Bernard W Balleine
BACKGROUND: High resolution neuronal information is extraordinarily useful in understanding the brain's functionality. The development of the Golgi-Cox stain allowed observation of the neuron in its entirety with unrivalled detail. Recently tissue clearing techniques, e.g., CLARITY and CUBIC, provide the potential to observe entire neuronal circuits intact within tissue and without previous restrictions with regard to section thickness. NEW METHOD: Here we describe an improved Golgi-Cox stain method, optimized for use with CLARITY and CUBIC, that stains within 48hrs and that can be used in both fresh and fixed tissue...
November 15, 2017: Journal of Neuroscience Methods
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