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https://www.readbyqxmd.com/read/29346838/first-in-human-study-to-assess-safety-pharmacokinetics-and-pharmacodynamics-of-bms-962212-a-direct-reversible-small-molecule-factor-xia-inhibitor-in-non-japanese-and-japanese-healthy-subjects
#1
Vidya Perera, Joseph M Luettgen, Zhaoqing Wang, Charles E Frost, Cynthia Yones, Cesare Russo, John Lee, Yue Zhao, Frank P LaCreta, Xuewen Ma, Robert M Knabb, Dietmar Seiffert, Mary DeSouza, Pierre Mugnier, Brenda Cirincione, Takayo Ueno, Robert J A Frost
AIMS: To assess the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of BMS-962212, a first-in-class Factor XIa inhibitor, in Japanese and non-Japanese healthy subjects. METHODS: This was a randomized, placebo-controlled, double-blind, sequential, ascending dose study of 2 hour (Part A) and 5 day (Part B) intravenous (IV) infusions of BMS-962212. Part A used 4 doses (1.5, 4, 10, and 25 mg h-1 ) assigned to BMS-962212 or placebo in a 3:1 ratio per dose. Part B used 4 doses (1, 3, 9, and 20 mg h-1 ) enrolling Japanese (n = 4 active, n = 1 placebo) and non-Japanese subjects (n = 4 active, n = 1 placebo) per dose...
January 18, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29346832/diagnosis-of-lumbar-spinal-stenosis-with-functional-myelography
#2
Matthias Morgalla, Sandra Frantz, Roberto Alexandre Dezena, Carlos Umberto Pereira, Marcos Tatagiba
BACKGROUND AND STUDY AIMS:  The diagnosis of a lumbar spinal stenosis demands advanced diagnostic radiologic techniques. In recent decades magnetic resonance imaging (MRI) has replaced myelography, now considered an old-fashioned technique. It was our hypothesis that functional myelography still plays an important role in selected cases. We investigated how our surgical strategy was influenced by the results of MRI, functional myelography, and postmyelography computed tomography (CT) in patients with a lumbar spinal stenosis...
January 18, 2018: Journal of Neurological Surgery. Part A, Central European Neurosurgery
https://www.readbyqxmd.com/read/29346831/postoperative-reduction-of-intraventricular-hemorrhage-volume-single-versus-dual-catheter-drainage
#3
Syed Shahzad Hussain, Asif Raza, Saman Shahid, Hafiz Hamza Asif, Usman Ahmad, Naveed Ashraf
BACKGROUND/AIMS:  The use of single/dual external ventricular drains (EVD) for reducing intraventricular hemorrhage (IVH) is under investigation. A randomized controlled trial was conducted to compare postoperative reduction of IVH volume using single- and dual-catheter drainage in spontaneous IVH patients. We investigated factors that may influence an effective hematoma volume reduction by EVDs. MATERIALS AND METHODS:  The average cerebrospinal fluid (CSF) drainage volumes were analyzed...
January 18, 2018: Journal of Neurological Surgery. Part A, Central European Neurosurgery
https://www.readbyqxmd.com/read/29346807/anti-angiogenic-activity-of-rotenoids-from-the-stems-of-derris-trifoliata
#4
Yanisa Mittraphab, Nattaya Ngamrojanavanich, Kuniyoshi Shimizu, Kiminori Matsubara, Khanitha Pudhom
The plants in the genus Derris have proven to be a rich source of rotenoids, of which cytotoxic effect against cancer cells seem to be pronounced. However, their effect on angiogenesis playing a crucial role in both cancer growth and metastasis has been seldom investigated. This study aimed at investigating the effect of the eight rotenoids (1: -8: ) isolated from Derris trifoliata stems on three cancer cells and angiogenesis. Among them, 12a-hydroxyrotenone (2: ) exhibited potent inhibition on both cell growth and migration of HCT116 colon cancer cells...
January 18, 2018: Planta Medica
https://www.readbyqxmd.com/read/29346801/early-gene-expression-profile-in-retinal-ganglion-cell-layer-after-optic-nerve-crush-in-mice
#5
Satoru Ueno, Azusa Yoneshige, Yoshiki Koriyama, Man Hagiyama, Yoshikazu Shimomura, Akihiko Ito
Purpose: Optic nerve crush (ONC) induces retinal ganglion cell (RGC) death, which causes vision loss in glaucoma. To investigate early events leading to apoptosis of RGCs, we performed gene expression analysis of injured retinas in the period before RGC loss. Methods: The temporal changes of gene profiles at 0, 1, and 4 days after ONC were determined by DNA microarray. To verify the gene expression changes in RGCs, we enriched RGCs by laser-captured microdissection and performed real-time RT-PCR of 14 selected genes...
January 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29346793/epicardial-fat-thickness-in-non-obese-neurologically-impaired-children-association-with-unfavorable-cardiometabolic-risk-profile
#6
Valeria Calcaterra, Hellas Cena, Pietro Mariano Casali, Gianluca Iacobellis, Riccardo Albertini, Mara De Amici, Annalisa de Silvestri, Calogero Comparato, Gloria Pelizzo
BACKGROUND: Cardiovascular risk is reported in disabled children and epicardial fat (EF) is considered an independent predictor of cardiovascular disease (CVD). No data on the EF thickness (EFT) evaluation in disabled children have been published. OBJECTIVE: We investigated EFT in neurologically impaired (NI) children; its relationship with their metabolic profile was also considered. METHODS: Clinical data, body composition estimation, biochemical profile, and ultrasound-measured EFT were performed in 32 disabled patients (12...
January 18, 2018: Annals of Nutrition & Metabolism
https://www.readbyqxmd.com/read/29346789/mentalization-and-self-efficacy-as-mediators-between-psychological-symptom-severity-and-disabilities-in-activities-and-participation-in-psychotherapy-patients
#7
Thomas Probst, Maria Dehoust, Anna Levke Brütt, Holger Schulz, Christoph Pieh, Sylke Andreas
BACKGROUND: Psychotherapy patients can be more or less disabled by their psychological symptoms. The present study investigated whether mentalization and self-efficacy contribute to the association between psychological symptom severity and disabilities in activities and participation. METHODS: The data of 216 psychotherapy inpatients were examined in a cross-sectional design. Bootstrapping-enhanced mediation analyses were performed to investigate whether self-efficacy and mentalization are mediators between psychological symptom severity and disabilities in activities and participation...
January 19, 2018: Psychopathology
https://www.readbyqxmd.com/read/29346784/surgical-treatment-and-chemotherapy-of-adult-primary-liver-sarcoma-experiences-from-a-single-hospital-in-china
#8
Feng Zhou, Han-Zhang Huang, Meng-Tao Zhou, Shao-Liang Han
BACKGROUND: The aim of this study is to improve the preoperative diagnostic accuracy and treatment results by investigating the clinical features and prognosis of primary liver sarcoma (PLS). METHODS: Clinical data, surgical treatments, adjuvant chemotherapy, and prognosis of 17 PLS patients whose diseases were pathologically confirmed were retrospectively analyzed. RESULTS: The main clinical symptoms included epigastric pain in 9 patients, epigastric distention in 7, and loss of appetite in 4; these symptoms were detected during the postoperative follow-up for gastric carcinoma in 1...
January 18, 2018: Digestive Surgery
https://www.readbyqxmd.com/read/29346762/transcriptome-and-dna-methylome-analysis-in-a-mouse-model-of-diet-induced-obesity-predicts-increased-risk-of-colorectal-cancer
#9
Ruifang Li, Sara A Grimm, Deepak Mav, Haiwei Gu, Danijel Djukovic, Ruchir Shah, B Alex Merrick, Daniel Raftery, Paul A Wade
Colorectal cancer (CRC) tends to occur at older age; however, CRC incidence rates have been rising sharply among young age groups. The increasing prevalence of obesity is recognized as a major risk, yet the mechanistic underpinnings remain poorly understood. Using a diet-induced obesity mouse model, we identified obesity-associated molecular changes in the colonic epithelium of young and aged mice, and we further investigated whether the changes were reversed after weight loss. Transcriptome analysis indicated that obesity-related colonic cellular metabolic switch favoring long-chain fatty acid oxidation happened in young mice, while obesity-associated downregulation of negative feedback regulators of pro-proliferative signaling pathways occurred in older mice...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29346758/size-dependent-axonal-bouton-dynamics-following-visual-deprivation-in%C3%A2-vivo
#10
Rosanna P Sammons, Claudia Clopath, Samuel J Barnes
Persistent synapses are thought to underpin the storage of sensory experience, yet little is known about their structural plasticity in vivo. We investigated how persistent presynaptic structures respond to the loss of primary sensory input. Using in vivo two-photon (2P) imaging, we measured fluctuations in the size of excitatory axonal boutons in L2/3 of adult mouse visual cortex after monocular enucleation. The average size of boutons did not change after deprivation, but the range of bouton sizes was reduced...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29346734/fluctuation-effects-on-the-brush-structure-of-mixed-brush-nanoparticles-in-solution
#11
Jason P Koski, Amalie L Frischknecht
A potentially attractive way to control nanoparticle assembly is to graft one or more polymers on the nanoparticle, to control the nanoparticle-nanoparticle interactions. When two immiscible polymers are grafted on the nanoparticle, they can microphase separate to form domains at the nanoparticle surface. Here we computationally investigate the phase behavior of such binary mixed brush nanoparticles in solution, across a large and experimentally relevant parameter space. Specifically, we calculate the mean-field phase diagram, assuming uniform grafting of the two polymers, as a function of the nanoparticle size relative to the length of the grafted chains, the grafting density, the enthalpic repulsion between the grafted chains, and the solvent quality...
January 18, 2018: ACS Nano
https://www.readbyqxmd.com/read/29346731/direct-polymerization-of-the-arsenic-drug-penao-to-obtain-nanoparticles-with-high-thiol-reactivity-and-anti-cancer-efficiency
#12
Janina-Miriam Noy, Hongxu Lu, Philip Hogg, Jia-Lin Yang, Martina H Stenzel
PENAO (4-(N-(S-penicillaminylacetyl)amino) phenylarsonous acid), which is a mitochondria inhibitor that reacts with adenine nucleotide translocator (ANT), is currently being trialed in patients with solid tumors. To increase the stability of the drug, the formation of nanoparticles has been proposed. Herein, the direct synthesis of polymeric micelles based on the anti-cancer drug PENAO is presented. PENAO is readily available for amidation reaction to form PENAO MA (4-(N-(S-penicillaminylacetyl) amino) phenylarsonous acid methacrylamide) which undergoes RAFT (reversible addition fragmentation chin transfer) polymerization with poly(polyethylene glycol methyl ether methacrylate) (PEGMA) as comonomer and poly(methylmethacrylate) (pMMA) as chain transfer agent, resulting in p(MMA)-b-p(PEG-co-PENAO) block copolymers with 3-15 wt...
January 18, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29346729/electronic-interactions-in-iminophosphorane-superbase-complexes-with-carbon-dioxide
#13
Francesca Ingrosso, Manuel F Ruiz-Lopez
Iminophosphoranes or phosphazenes are an important class of compounds with increasing use in synthetic organic chemistry as neutral organic superbases exhibiting low nucleophilicity. Their electronic structure and therefore their properties strongly depend on substitution but there have been very few theoretical studies devoted to this topic, and more specifically to the formation of electron donor-acceptor complexes of iminophosphoranes with electrophiles. In this work, we have investigated the interaction with carbon dioxide at different ab initio levels...
January 18, 2018: Journal of Physical Chemistry. A
https://www.readbyqxmd.com/read/29346716/neuropeptide-af-induces-piecemeal-degranulation-in-murine-mucosal-mast-cells-a-new-mediator-in-neuro-immune-communication-in-the-intestinal-lamina-propria
#14
Nada Abdellah, Samuel Van Remoortel, Omnia Mohey-Elsaeed, Mohamed-Nabil Mostafa, Yasser A Ahmed, Jean-Pierre Timmermans, Roeland Buckinx
Neuropeptides AF (NPAF), FF (NPFF) and SF (NPSF) are RFamide neuropeptides known to be widely expressed in the mammalian central nervous system, where they fulfill a wide range of functions with pain modulation being the most prominent one. Recent evidence indicates that RFamides act as mediators in mast cell-sensory nerve communications related to allergic disease. Previous work by our group has shown that the expression levels of some members of the Mas-related gene receptor (Mrgpr) family in both enteric neurons and mucosal mast cells change during intestinal inflammation...
January 18, 2018: Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology
https://www.readbyqxmd.com/read/29346712/synergetic-effects-of-prenatal-and-postnatal-high-sucrose-intake-on-glucose-tolerance-and-hepatic-insulin-resistance-in-rat-offspring
#15
Pengjie Zhang, Di Zhu, Yueming Zhang, Lingjun Li, Xionghui Chen, Wenna Zhang, Ruixiu Shi, Jianying Tao, Bing Han, Zhice Xu
SCOPE: High sucrose intake during pregnancy is linked to type 2 diabetes mellitus and altered insulin resistance. METHODS AND RESULTS: This study attempted to ascertain whether prenatal high sucrose intake (20% sucrose) alleviates the detrimental effects of high postnatal sugar consumption in the offspring, and the molecular mechanisms were investigated using a rat model. High prenatal sucrose exposure increased the body weight of the offspring at 1 to 3 weeks of age...
January 18, 2018: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29346691/the-impact-of-near-peer-teaching-on-medical-students-transition-to-clerkships
#16
Alexander C Knobloch, Christy J W Ledford, Sean Wilkes, Adam K Saperstein
BACKGROUND AND OBJECTIVES: The transition to clerkships is one of the most challenging times during medical school. To help students better cope, many schools have established transition-to-clerkship curricula. Such curricula may optimally prepare students through increasing their self-efficacy and response efficacy. We hypothesized that a small-group, near-peer-led format would be ideally suited to help students achieve these outcomes. METHODS: During process improvement for a transition-to-clerkship curriculum, we conducted an informal focus group and subsequent survey of postclerkship students to guide curricular innovation, including incorporation of third- and fourth-year students as near-peer instructors in a seminar format...
January 2018: Family Medicine
https://www.readbyqxmd.com/read/29346681/optimal-number-and-sizes-of-the-doses-in-fractionated-radiotherapy-according-to-the-lq-model
#17
C Bruni, F Conte, F Papa, C Sinisgalli
We address a non-linear programming problem to find the optimal scheme of dose fractionation in cancer radiotherapy. Using the LQ model to represent the response to radiation of tumour and normal tissues, we formulate a constrained non-linear optimization problem in terms of the variables number and sizes of the dose fractions. Quadratic constraints are imposed to guarantee that the damages to the early and late responding normal tissues do not exceed assigned tolerable levels. Linear constraints are set to limit the size of the daily doses...
January 15, 2018: Mathematical Medicine and Biology: a Journal of the IMA
https://www.readbyqxmd.com/read/29346677/anatomical-explanations-for-acute-depressions-in-radial-pattern-of-axial-sap-flow-in-two-diffuse-porous-mangrove-species-implications-for-water-use
#18
Hewei Zhao, Shengchang Yang, Xudong Guo, Congjiao Peng, Xiaoxuan Gu, Chuanyuan Deng, Luzhen Chen
Mangrove species have developed uniquely efficient water-use strategies in order to survive in highly saline and anaerobic environments. Herein, we estimated the stand water use of two diffuse-porous mangrove species of the same age, Sonneratia apetala Buch. Ham and Sonneratia caseolaris (L.) Engl., growing in a similar intertidal environment. Specifically, to investigate the radial patterns of axial sap flow density (Js) and understand the anatomical traits associated with them, we measured axial sap flow density in situ together with micromorphological observations...
January 16, 2018: Tree Physiology
https://www.readbyqxmd.com/read/29346671/hematological-analysis-in-thai-samples-with-deletional-and-nondeletional-hbh-diseases
#19
Sakorn Pornprasert, Nur-Afsan Salaeh, Monthathip Tookjai, Manoo Punyamung, Panida Pongpunyayuen, Kallayanee Treesuwan
Objectives: To compare hematological parameters between deletional and nondeletional HbH diseases, and to investigate the correlation between HbH levels and hematological parameters within these 2 groups. Methods: Samples of 43 deletional HbH diseases, which included 39 --SEA/-α3.7, 4 - -SEA/-α4.2, and 22 nondeletional HbH diseases (- -SEA/αcsα), were used in this study. Correlations between HbH levels and hematological parameters within these 2 groups were analyzed...
January 13, 2018: Laboratory Medicine
https://www.readbyqxmd.com/read/29346650/persistence-of-zika-virus-after-birth-clinical-virological-neuroimaging-and-neuropathological-documentation-in-a-5-month-infant-with-congenital-zika-syndrome
#20
Leila Chimelli, Sheila Moura Pone, Elyzabeth Avvad-Portari, Zilton Farias Meira Vasconcelos, Andrea Araújo Zin, Daniela Prado Cunha, Nathalia Raposo Thompson, Maria Elisabeth Lopes Moreira, Clayton A Wiley, Marcos Vinicius da Silva Pone
During the Zika epidemic in Brazil, a baby was born at term with microcephaly and arthrogryposis. The mother had Zika symptoms at 10 weeks of gestation. At 17 weeks, ultrasound showed cerebral malformation and ventriculomegaly. At 24 weeks, the amniotic fluid contained ZIKV RNA and at birth, placenta and maternal blood were also positive using RT-qPCR. At birth the baby urine contained ZIKV RNA, whereas CSF at birth and urine at 17 days did not. Seizures started at 6 days. EEG was abnormal and CT scan showed cerebral atrophy, calcifications, lissencephaly, ventriculomegaly, and cerebellar hypoplasia...
January 13, 2018: Journal of Neuropathology and Experimental Neurology
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