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https://www.readbyqxmd.com/read/28636208/a-phase-i-trial-of-prn1008-a-novel-reversible-covalent-inhibitor-of-bruton-s-tyrosine-kinase-in-healthy-volunteers
#1
Patrick F Smith, Janakan Krishnarajah, Philip A Nunn, Ron J Hill, Dane Karr, D Tam, Mohammad Masjedizadeh, Jens O Funk, Steve G Gourlay
AIM: To evaluate the safety, tolerability, and PK/PD of PRN1008, a novel BTK inhibitor, in healthy volunteers, and thus determine the dose range for future clinical studies. METHODS: This was a two-part randomized, placebo controlled study in healthy volunteers using a liquid formulation. Part I was a single ascending dose design with dose levels of 50 to 1200 mg (n=6 active, 2 placebo per cohort); Part II was a multiple ascending dose design, with dose regimens ranging from 300 mg to 900 mg daily, either qd or bd for 10 days...
June 21, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28636185/decarboxylative-alkynylation
#2
Joel M Smith, Tian Qin, Rohan R Merchant, Jacob T Edwards, Lara R Malins, Zhiqing Liu, Guanda Che, Zichao Shen, Scott A Shaw, Martin D Eastgate, Phil S Baran
The development of a new decarboxylative cross-coupling protocol that affords terminal and substituted alkynes from various carboxylic acids is described using both nickel- and iron-based catalysts. The use of N-hydroxytetrachlorophthalimide (TCNHPI) esters is crucial to the success of the transformation, and the reaction is amenable to in situ carboxylic acid activation. Additionally, an inexpensive, commercially-available alkyne source is employed in this formal homologation process that serves as a surrogate for other well-established alkyne syntheses...
June 21, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28636072/using-chief-complaint-in-addition-to-diagnosis-codes-to-identify-falls-in-the-emergency-department
#3
Brian W Patterson, Maureen A Smith, Michael D Repplinger, Michael S Pulia, James E Svenson, Michael K Kim, Manish N Shah
OBJECTIVES: To compare incidence of falls in an emergency department (ED) cohort using a traditional International Classification of Diseases, Ninth Revision (ICD-9) code-based scheme and an expanded definition that included chief complaint information and to examine the clinical characteristics of visits "missed" in the ICD-9-based scheme. DESIGN: Retrospective electronic record review. SETTING: Academic medical center ED. PARTICIPANTS: Individuals aged 65 and older seen in the ED between January 1, 2013, and September 30, 2015...
June 21, 2017: Journal of the American Geriatrics Society
https://www.readbyqxmd.com/read/28635619/on-the-importance-of-accurate-quantification-of-individual-volatile-metabolites-in-exhaled-breath
#4
David Smith, Patrik Spanel
It is argued that shortcomings of certain approaches to breath analysis research based on superficial interpretation of non-quantitative data are inadvertently inhibiting the progression of non-invasive breath analysis into clinical practice. The objective of this perspective is to suggest more clinically profitable approaches to breath research. Thus, following a discourse on the challenges and expectations in breath research, a brief indication is given of the analytical techniques currently used for the analysis of very humid exhaled breath...
June 21, 2017: Journal of Breath Research
https://www.readbyqxmd.com/read/28635381/provoked-eagle-syndrome-after-dental-procedure-a-review-of-the-literature
#5
Shuo Li, Neeraj Blatt, Jubin Jacob, Nishant Gupta, Yogesh Kumar, Scott Smith
Eagle syndrome is an uncommon condition caused by an elongated ossified styloid process. The majority of individuals with an elongated ossified styloid process are asymptomatic. Therefore, this condition is diagnosed based on clinical presentation, with radiologic imaging serving to confirm the diagnosis. The styloid process is considered elongated if measuring greater than 3 cm, but there is little correlation between length of the styloid process and severity of symptoms. This syndrome was originally described in post-tonsillectomy patients, but has since been seen in other clinical settings...
January 1, 2017: Neuroradiology Journal
https://www.readbyqxmd.com/read/28634805/comparative-prevalence-of-escherichia-coli-carrying-virulence-genes-and-class-1-and-2-integrons-in-sub-tropical-and-cool-temperate-freshwater
#6
Jatinder P S Sidhu, Paul Jagals, Amy Smith, Simon Toze
Aquatic environments are now recognized secondary habitat of potentially pathogenic Escherichia coli. In this study, PCR-based analyses were used to determine the phylogenetic composition and frequency of occurrence of eight clinically significant virulence genes (VGs) in E. coli isolates from sub-tropical Brisbane and cool temperate Tasmania freshwater in Australia. In Brisbane, non-commensal E. coli isolates belonging to the B2 and D phylogenetic group were dominant (72%). A significantly higher number (P < 0...
June 21, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28634743/comminuted-olecranon-fractures-biomechanical-testing-of-locked-versus-minifragment-non-locked-plate-fixation
#7
David S Wellman, Scott M Tucker, Josh R Baxter, Nadine C Pardee, Lionel E Lazaro, Christopher S Smith, Dean G Lorich, David L Helfet
INTRODUCTION: Open reduction and internal fixation has long been accepted as optimal treatment for displaced olecranon fractures based on poor results seen with conservative management. With the presence of comminution, tension-band wiring constructs are contraindicated due to tendency to compress through fragments, thereby shortening the articular segment. Therefore, plate fixation is typically employed. Our hypothesis was that in a comminuted fracture model, 2.7 mm reconstruction plating without locking screws will perform equally to 3...
June 20, 2017: Archives of Orthopaedic and Trauma Surgery
https://www.readbyqxmd.com/read/28634656/patient-reported-eortc-qlq-cipn20-versus-physician-reported-ctcae-quantification-of-oxaliplatin-and-paclitaxel-carboplatin-induced-peripheral-neuropathy-in-ncctg-alliance-clinical-trials
#8
Jennifer Le-Rademacher, Rahul Kanwar, Drew Seisler, Deirdre R Pachman, Rui Qin, Alexej Abyzov, Kathryn J Ruddy, Michaela S Banck, Ellen M Lavoie Smith, Susan G Dorsey, Neil K Aaronson, Jeff Sloan, Charles L Loprinzi, Andreas S Beutler
PURPOSE: Clinical practice guidelines on chemotherapy-induced peripheral neuropathy (CIPN) use the NCI Common Terminology Criteria for Adverse Events (CTCAE), while recent clinical trials employ a potentially superior measure, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-CIPN twenty-item scale (QLQ-CIPN20), a patient-reported outcome (PRO). Practitioners and researchers lack guidance, regarding how QLQ-CIPN20 results relate to the traditional CTCAE during the serial assessment of patients undergoing chemotherapy...
June 20, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/28634611/micro-and-nano-patterned-conductive-graphene-peg-hybrid-scaffolds-for-cardiac-tissue-engineering
#9
Alec S T Smith, Hyok Yoo, Hyunjung Yi, Eun Hyun Ahn, Justin H Lee, Guozheng Shao, Ekaterina Nagornyak, Michael A Laflamme, Charles E Murry, Deok-Ho Kim
A lack of electrical conductivity and structural organization in currently available biomaterial scaffolds limits their utility for generating physiologically representative models of functional cardiac tissue. Here we report on the development of scalable, graphene-functionalized topographies with anisotropic electrical conductivity for engineering the structural and functional phenotypes of macroscopic cardiac tissue constructs. Guided by anisotropic electroconductive and topographic cues, the tissue constructs displayed structural property enhancement in myofibrils and sarcomeres, and exhibited significant increases in the expression of cell-cell coupling and calcium handling proteins, as well as in action potential duration and peak calcium release...
June 21, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28634574/reducing-viability-bias-in-analysis-of-gut-microbiota-in-preterm-infants-at-risk-of-nec-and-sepsis
#10
Gregory R Young, Darren L Smith, Nicholas D Embleton, Janet E Berrington, Edward C Schwalbe, Stephen P Cummings, Christopher J van der Gast, Clare Lanyon
Necrotising enterocolitis (NEC) and sepsis are serious diseases of preterm infants that can result in feeding intolerance, the need for bowel resection, impaired physiological and neurological development, and high mortality rates. Neonatal healthcare improvements have allowed greater survival rates in preterm infants leading to increased numbers at risk of developing NEC and sepsis. Gut bacteria play a role in protection from or propensity to these conditions and have therefore, been studied extensively using targeted 16S rRNA gene sequencing methods...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28634500/stroke-performance-measures-do-not-predict-functional-outcome
#11
Eric E Adelman, Lynda D Lisabeth, Melinda A Smith, Jonggyu Baek, Erin C Case, Brisa N Sánchez, James F Burke, Lesli E Skolarus, Darin B Zahuranec, William J Meurer, Devin L Brown, Kevin A Kerber, Deborah A Levine, Nelda M Garcia, Morgan S Campbell, Lewis B Morgenstern
BACKGROUND AND PURPOSE: Poststroke functional outcome is critical to stroke survivors. We sought to determine whether adherence to current stroke performance measures is associated with better functional outcome 90 days after an ischemic stroke. METHODS: Utilizing the Brain Attack Surveillance in Corpus Christi cohort, we examined adherence to 7 ischemic stroke performance measures from February 2009 to June 2012. Adherence to the measures was analyzed in aggregate using a binary defect-free score and an opportunity score, representing the proportion of eligible measures met...
July 2017: Neurohospitalist
https://www.readbyqxmd.com/read/28634479/whole-blood-profiling-of-bacillus-calmette-gu%C3%A3-rin-induced-trained-innate-immunity-in-infants-identifies-epidermal-growth-factor-il-6-platelet-derived-growth-factor-ab-bb-and-natural-killer-cell-activation
#12
Steven G Smith, Johanneke Kleinnijenhuis, Mihai G Netea, Hazel M Dockrell
Vaccination of infants with bacillus Calmette-Guérin (BCG) activates both the innate and adaptive arms of the immune response. The antimycobacterial effects of these responses most likely account for the ability of BCG to protect against childhood forms of tuberculosis (TB). There is also evidence for a heterologous protective effect of BCG vaccination against TB-unrelated mortality in low birth weight infants. A possible mechanism of action of this effect, the induction of trained innate immunity, has been demonstrated when cells from BCG-vaccinated adults are restimulated in vitro with non-related microbial stimuli...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28634475/cesarean-or-vaginal-birth-does-not-impact-the-longitudinal-development-of-the-gut-microbiome-in-a-cohort-of-exclusively-preterm-infants
#13
Christopher J Stewart, Nicholas D Embleton, Elizabeth Clements, Pamela N Luna, Daniel P Smith, Tatiana Y Fofanova, Andrew Nelson, Gillian Taylor, Caroline H Orr, Joseph F Petrosino, Janet E Berrington, Stephen P Cummings
The short and long-term impact of birth mode on the developing gut microbiome in neonates has potential implications for the health of infants. In term infants, the microbiome immediately following birth across multiple body sites corresponds to birth mode, with increased Bacteroides in vaginally delivered infants. We aimed to determine the impact of birth mode of the preterm gut microbiome over the first 100 days of life and following neonatal intensive care unit (NICU) discharge. In total, 867 stool samples from 46 preterm infants (21 cesarean and 25 vaginal), median gestational age 27 weeks, were sequenced (V4 region 16S rRNA gene, Illumina MiSeq)...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28634254/widespread-paleopolyploidy-gene-tree-conflict-and-recalcitrant-relationships-among-the-carnivorous-caryophyllales
#14
Joseph F Walker, Ya Yang, Michael J Moore, Jessica Mikenas, Alfonso Timoneda, Samuel F Brockington, Stephen A Smith
PREMISE OF STUDY: The carnivorous members of the large, hyperdiverse Caryophyllales (e.g., Venus flytrap, sundews, and Nepenthes pitcher plants) represent perhaps the oldest and most diverse lineage of carnivorous plants. However, despite numerous studies seeking to elucidate their evolutionary relationships, the early-diverging relationships remain unresolved. METHODS: To explore the utility of phylogenomic data sets for resolving relationships among the carnivorous Caryophyllales, we sequenced 10 transcriptomes, including all the carnivorous genera except those in the rare West African liana family Dioncophyllaceae...
June 20, 2017: American Journal of Botany
https://www.readbyqxmd.com/read/28634240/leucine-biosynthesis-is-involved-in-regulating-high-lipid-accumulation-in-yarrowia-lipolytica
#15
Eduard J Kerkhoven, Young-Mo Kim, Siwei Wei, Carrie D Nicora, Thomas L Fillmore, Samuel O Purvine, Bobbie-Jo Webb-Robertson, Richard D Smith, Scott E Baker, Thomas O Metz, Jens Nielsen
The yeast Yarrowia lipolytica is a potent accumulator of lipids, and lipogenesis in this organism can be influenced by a variety of factors, such as genetics and environmental conditions. Using a multifactorial study, we elucidated the effects of both genetic and environmental factors on regulation of lipogenesis in Y. lipolytica and identified how two opposite regulatory states both result in lipid accumulation. This study involved comparison of a strain overexpressing diacylglycerol acyltransferase (DGA1) with a control strain grown under either nitrogen or carbon limitation conditions...
June 20, 2017: MBio
https://www.readbyqxmd.com/read/28634199/characterising-cis-regulatory-variation-in-the-transcriptome-of-histologically-normal-and-tumour-derived-pancreatic-tissues
#16
Mingfeng Zhang, Soren Lykke-Andersen, Bin Zhu, Wenming Xiao, Jason W Hoskins, Xijun Zhang, Lauren M Rost, Irene Collins, Martijn van de Bunt, Jinping Jia, Hemang Parikh, Tongwu Zhang, Lei Song, Ashley Jermusyk, Charles C Chung, Bin Zhu, Weiyin Zhou, Gail L Matters, Robert C Kurtz, Meredith Yeager, Torben Heick Jensen, Kevin M Brown, Halit Ongen, William R Bamlet, Bradley A Murray, Mark I McCarthy, Stephen J Chanock, Nilanjan Chatterjee, Brian M Wolpin, Jill P Smith, Sara H Olson, Gloria M Petersen, Jianxin Shi, Laufey Amundadottir
OBJECTIVE: To elucidate the genetic architecture of gene expression in pancreatic tissues. DESIGN: We performed expression quantitative trait locus (eQTL) analysis in histologically normal pancreatic tissue samples (n=95) using RNA sequencing and the corresponding 1000 genomes imputed germline genotypes. Data from pancreatic tumour-derived tissue samples (n=115) from The Cancer Genome Atlas were included for comparison. RESULTS: We identified 38 615 cis-eQTLs (in 484 genes) in histologically normal tissues and 39 713 cis-eQTL (in 237 genes) in tumour-derived tissues (false discovery rate <0...
June 20, 2017: Gut
https://www.readbyqxmd.com/read/28634166/development-and-validation-of-the-pediatric-medical-complexity-algorithm-pmca-version-2-0
#17
Tamara D Simon, Mary Lawrence Cawthon, Jean Popalisky, Rita Mangione-Smith
BACKGROUND AND OBJECTIVES: The Pediatric Medical Complexity Algorithm (PMCA) was developed to stratify children by level of medical complexity. We sought to refine PMCA and evaluate its performance based on the duration of eligibility and completeness of Medicaid data. METHODS: PMCA version 1.0 was applied to a cohort of 299 children insured by Washington State Medicaid with ≥1 Seattle Children's Hospital outpatient, emergency department, and/or inpatient encounter in 2012...
June 20, 2017: Hospital Pediatrics
https://www.readbyqxmd.com/read/28634025/impaired-cerebral-autoregulation-in-preoperative-newborn-infants-with-congenital-heart-disease
#18
Jodie K Votava-Smith, Christopher J Statile, Michael D Taylor, Eileen C King, Jesse M Pratt, David P Nelson, Erik C Michelfelder
OBJECTIVES: To characterize cerebral autoregulation (CA) in preoperative newborn infants with congenital heart disease (CHD). METHODS: This was a prospective, pilot study of term newborns with CHD who required intensive care. Continuous mean arterial blood pressure (MAP), cerebral tissue oxygen saturation (SCTO2) via near-infrared spectroscopy, and arterial oxygen saturation (SaO2) were collected. Significant low-frequency coherence between MAP and SCTO2 was used to define impaired CA in 20-minute epochs...
May 23, 2017: Journal of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/28633549/an-update-on-zika-vaccine-developments
#19
Anna Durbin, Annelies Wilder-Smith
The devastating consequences of congenital Zika virus (ZIKV) infection led to a global response directed toward a better understanding of the epidemiology and pathogenesis of ZIKV and to efforts at vaccine development. As a result, there are currently 45 ZIKV vaccine candidates in development. Areas covered: Both traditional (purified inactivated, live attenuated, viral-vectored, recombinant sub-unit) and novel (DNA, self-replicating RNA, mRNA) vaccine platforms are being utilized. For emergency use, vaccines that are appropriate for women of child-bearing age (including pregnant women) are being developed...
June 21, 2017: Expert Review of Vaccines
https://www.readbyqxmd.com/read/28633501/epidemiology-of-pediatric-multidrug-resistant-tuberculosis-in-the-united-states-1993-2014
#20
Sarah E Smith, Robert Pratt, Lisa Trieu, Pennan M Barry, Dzung T Thai, Shama Desai Ahuja, Sarita Shah
Background: Multidrug-resistant tuberculosis (MDR TB) is an important global public health threat, but accurate estimates of MDR TB burden among children are lacking. Methods: We analyzed demographic, clinical and laboratory data for newly-diagnosed pediatric (<15 years) TB cases reported to the US National TB Surveillance System (NTSS) during 1993-2014. MDR TB was defined as culture-confirmed TB disease with resistance to at least isoniazid and rifampicin. To ascertain potential under-estimation of pediatric MDR TB, we surveyed high burden states for clinically-diagnosed cases treated for MDR TB...
June 19, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
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