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Murad Megjhani, Kalijah Terilli, Andrew Martin, Angela Velazquez, Jan Claassen, David Roh, Sachin Agarwal, Peter Smielewski, Amelia K Boehme, J Michael Schmidt, Soojin Park
OBJECTIVE: The objective was to explore the validity of industry-parameterized vital signs in the generation of pressure reactivity index (PRx) and optimal cerebral perfusion pressure (CPPopt) values. MATERIALS AND METHODS: Ten patients with intracranial pressure (ICP) monitors from 2008 to 2013 in a tertiary care hospital were included. Arterial blood pressure (ABP) and ICP were sampled at 240 Hz (of waveform data) and 0.2 Hz (of parameterized data produced by heuristic industry proprietary algorithms)...
2018: Acta Neurochirurgica. Supplement
Antonio Bruni, Andrew R Pepper, Rena L Pawlick, Boris Gala-Lopez, Anissa Gamble, Tatsuya Kin, Andrew J Malcolm, Carissa Jones, Jon D Piganelli, James D Crapo, A M James Shapiro
Islet transplantation has become a well-established therapy for select patients suffering from type 1 diabetes. Viability and engraftment can be compromised by the generation of oxidative stress encountered during isolation and culture. We evaluate whether administration of BMX-001, and its earlier derivative, BMX-010 could improve islet function and engraftment outcomes. Long-term culture of human islets with BMX-001, but not BMX-010, exhibited preserved in vitro viability. Murine islets isolated and cultured for 24 hours with 34μM BMX-001 exhibited improved insulin secretion (n=3 isolations, p<0...
February 21, 2018: American Journal of Transplantation
Shih-Chang Hsueh, Kai-Yun Chen, Jing-Huei Lai, Chung-Che Wu, Yu-Wen Yu, Yu Luo, Tsung-Hsun Hsieh, Yung-Hsiao Chiang
BACKGROUND: Parkinson's disease (PD) is typically characterized by impairment of motor function. Gait disturbances similar to those observed in patients with PD can be observed in animals after injection of neurotoxin 6-hydroxydopamine (6-OHDA) to induce unilateral nigrostriatal dopamine depletion. Exercise has been shown to be a promising non-pharmacological approach to reduce the risk of neurodegenerative disease. METHODS: In this study, we investigated the long-term effects of voluntary running wheel exercise on gait phenotypes, depression, cognitive, rotational behaviors as well as histology in a 6-OHDA-lesioned rat model of PD...
February 8, 2018: International Journal of Molecular Sciences
Ettore Palma, Nadia Recine, Lavinia Domenici, Margherita Giorgini, Alessandra Pierangeli, Pierluigi Benedetti Panici
BACKGROUND: Over recent years, a growing interest has developed in microbiota and in the concept of maintaining a special balance between Lactobacillus and other bacteria species in order to promote women's well-being. The aim of our study was to confirm that vaginal Lactobacilli long-lasting implementation in women with HPV-infections and concomitant bacterial vaginosis or vaginitis might be able to help in solving the viral infection, by re-establishing the original eubiosis. METHODS: A total of 117 women affected by bacterial vaginosis or vaginitis with concomitant HPV-infections were enrolled at Department of Gynecological Obstetrics and Urological Sciences, La Sapienza University, Rome, Italy between February 2015 and March 2016...
January 5, 2018: BMC Infectious Diseases
Jolieke G van Oosterwijk, Daelynn R Buelow, Christina D Drenberg, Aksana Vasilyeva, Lie Li, Lei Shi, Yong-Dong Wang, David Finkelstein, Sheila A Shurtleff, Laura J Janke, Stanley Pounds, Jeffrey E Rubnitz, Hiroto Inaba, Navjotsingh Pabla, Sharyn D Baker
Oncogenic addiction to the Fms-like tyrosine kinase 3 (FLT3) is a hallmark of acute myeloid leukemia (AML) that harbors the FLT3-internal tandem duplication (FLT3-ITD) mutation. While FLT3 inhibitors like sorafenib show initial therapeutic efficacy, resistance rapidly develops through mechanisms that are incompletely understood. Here, we used RNA-Seq-based analysis of patient leukemic cells and found that upregulation of the Tec family kinase BMX occurs during sorafenib resistance. This upregulation was recapitulated in an in vivo murine FLT3-ITD-positive (FLT3-ITD+) model of sorafenib resistance...
January 2, 2018: Journal of Clinical Investigation
Qiongyao Wang, Fanrui Zeng, Yanqin Sun, Qianqian Qiu, Jian Zhang, Weimei Huang, Jie Huang, Xiaomin Huang, Linlang Guo
Purpose: Epithelial and endothelial tyrosine kinase (Etk), also known as bone marrow X kinase (Bmx), was found to be critical in modulating the chemoresistance of small-cell lung cancer (SCLC) in our preliminary study. However, the molecular mechanisms of Etk in SCLC chemoresistance remain poorly understood. Experimental Design: We determined correlation of Etk with autophagy in SCLC. And direct inhibition of autophagy was performed to validate its effect on chemoresistance. Coimmunoprecipitation (co-IP) and GST-pull down experiments were conducted to verify the interaction of Etk and PFKFB4, after a microarray analysis...
February 15, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Josephine Grigg, Eric Haakonssen, Evelyne Rathbone, Robin Orr, Justin W L Keogh
The aim of this study was to quantify the validity and intra-tester reliability of a novel method of kinematic measurement. The measurement target was the joint angles of an athlete performing a BMX Supercross (SX) gate start action through the first 1.2 s of movement in situ on a BMX SX ramp using a standard gate start procedure. The method employed GoPro® Hero 4 Silver (GoPro Inc., USA) cameras capturing data at 120 fps 720 p on a 'normal' lens setting. Kinovea 0.8.15 (, France) was used for analysis...
November 13, 2017: Sports Biomechanics
Wenchao Zhou, Cong Chen, Yu Shi, Qiulian Wu, Ryan C Gimple, Xiaoguang Fang, Zhi Huang, Kui Zhai, Susan Q Ke, Yi-Fang Ping, Hua Feng, Jeremy N Rich, Jennifer S Yu, Shideng Bao, Xiu-Wu Bian
The blood-tumor barrier (BTB) is a major obstacle for drug delivery to malignant brain tumors such as glioblastoma (GBM). Disrupting the BTB is therefore highly desirable but complicated by the need to maintain the normal blood-brain barrier (BBB). Here we show that targeting glioma stem cell (GSC)-derived pericytes specifically disrupts the BTB and enhances drug effusion into brain tumors. We found that pericyte coverage of tumor vasculature is inversely correlated with GBM patient survival after chemotherapy...
November 2, 2017: Cell Stem Cell
Torbjørn Soligard, Kathrin Steffen, Debbie Palmer, Juan Manuel Alonso, Roald Bahr, Alexandre Dias Lopes, Jiri Dvorak, Marie-Elaine Grant, Willem Meeuwisse, Margo Mountjoy, Leonardo Oliveira Pena Costa, Natalia Salmina, Richard Budgett, Lars Engebretsen
OBJECTIVE: To describe the pattern of injuries and illnesses sustained during the Games of the XXXI Olympiad, hosted by Rio de Janeiro from 5 to 21 August 2016. METHODS: We recorded the daily incidence of athlete injuries and illnesses (1) through the reporting of all National Olympic Committee (NOC) medical teams and (2) in the polyclinic and medical venues by the Rio 2016 medical staff. RESULTS: In total, 11 274 athletes (5089 women, 45%; 6185 men, 55%) from 207 NOCs participated in the study...
September 2017: British Journal of Sports Medicine
Linhong He, Da Li, Chufeng Zhang, Peng Bai, Lijuan Chen
Described as a Btk inhibitor, ibrutinib also potently inhibits Bmx and EGFR, two good targets for lung cancer. Owing to its high CLogP (4.07) and low aqueous solubility (<0.01mg/ml), resulting in unfavorable bioavailability, ibrutinib requires high dosages to achieve good clinical response in the treatment of non-small cell lung cancer (NSCLC). In our effort to improve the CLogP of ibrutinib by structural optimization led to the discovery of a potent anti-cancer agent B6, with beneficial physicochemical parameters (CLogP=2...
September 1, 2017: Bioorganic & Medicinal Chemistry Letters
Wei Xu, Fengtao Luo, Quan Wang, Qiaoyan Tan, Junlan Huang, Siru Zhou, Zuqiang Wang, Xianding Sun, Liang Kuang, Min Jin, Nan Su, Wanling Jiang, Liang Chen, Huabing Qi, Ying Zhu, Bo Chen, Hangang Chen, Shuai Chen, Yu Gao, Xiaoling Xu, Chuxia Deng, Lin Chen, Yangli Xie, Xiaolan Du
Apert syndrome is one of the most severe craniosynostoses, resulting from gain-of-function mutations in fibroblast growth factor receptor 2 (FGFR2). Previous studies have shown that gain-of-function mutations of FGFR2 (S252W or P253R) cause skull malformation of human Apert syndrome by affecting both chondrogenesis and osteogenesis, underscoring the key role of FGFR2 in bone development. However, the effects of FGFR2 on bone formation at the adult stage have not been fully investigated. To investigate the role of FGFR2 in bone formation, we generated mice with tamoxifen-inducible expression of mutant FGFR2 (P253R) at the adult stage...
November 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
J Molina-Cerrillo, T Alonso-Gordoa, P Gajate, E Grande
Bruton's tyrosine kinase (BTK) is a non-receptor intracellular kinase that belongs to the TEC-family tyrosine kinases together with bone marrow-expressed kinase (BMX), redundant-resting lymphocyte kinase (RLK), and IL-2 inducible T-Cell kinase (ITK). All these proteins play a key role in the intracellular signaling of both B and T lymphocytes. Recently, some preclinical data have demonstrated that BTK is present in certain tumor subtypes and in other relevant cells that are contributing to the tumor microenvironment such as dendritic cells, macrophages, myeloid derived suppressor cells and endothelial cells...
July 2017: Cancer Treatment Reviews
Guiqiu Zhang, Lei Fu, Hong Li, Xuchan Fan, Dezhan Chen
The bonding between noble gas and noble metal halide like hydrogen bonding (H-bonding) motivates us to investigate the bonding mechanism and the bonding covalency in NgMX (Ng = He, Ne, Ar, Kr, Xe, Rn; M = Cu, Ag, Au; X = F, Cl, Br, I) complexes using natural bond orbital (NBO) and natural resonance theory (NRT) methods. In this study, we introduce the new resonance bonding model in H-bonding into NgMX bonding. We provide strong evidence for resonance bonding involving two important resonance structures: Ng: M-X ↔ Ng(+)-M :X(-) in each of NgMX complexes, originating in the nNg → σ*MX hyperconjugative interaction...
July 3, 2017: Journal of Physical Chemistry. A
Beilei Wang, Yuanxin Deng, Yongfei Chen, Kailin Yu, Aoli Wang, Qianmao Liang, Wei Wang, Cheng Chen, Hong Wu, Chen Hu, Weili Miao, Wooyoung Hur, Wenchao Wang, Zhenquan Hu, Ellen L Weisberg, Jinhua Wang, Tao Ren, Yinsheng Wang, Nathanael S Gray, Qingsong Liu, Jing Liu
Through a structure-based drug design approach, a tricyclic benzonaphthyridinone pharmacophore was used as a starting point for carrying out detailed medicinal structure-activity relationhip (SAR) studies geared toward characterization of a panel of proposed BTK inhibitors, including 6 (QL-X-138), 7 (BMX-IN-1) and 8 (QL47). These studies led to the discovery of the novel potent irreversible BTK inhibitor, compound 18 (CHMFL-BTK-11). Kinetic analysis of compound 18 revealed an irreversible binding efficacy (kinact/Ki) of 0...
September 8, 2017: European Journal of Medicinal Chemistry
Howard T Hurst, Lee Rylands, Stephen Atkins, Kevin Enright, Simon J Roberts
OBJECTIVES: To investigate the influence of BMX helmets and neck braces on translational and rotational accelerations in youth riders. DESIGN: Mixed model, repeated measure and correlation. METHODS: Twenty three competitive youth BMX riders classified by age group (6-9 years, 10-13 years and 14-18 years) completed 6 laps of an indoor BMX track at race pace, 3 laps without a neck brace (NB) and 3 without brace (WB). A triaxial accelerometer with gyroscope was placed behind the right ear to determine the mean number of accelerations, translational and rotational, of the head between conditions and by age group...
May 25, 2017: Journal of Science and Medicine in Sport
Yuanyuan Li, Nan Cui, Peng-Sheng Zheng, Wen-Ting Yang
Bone marrow X-linked kinase (BMX, also known as Etk) has been reported to be involved in cell proliferation, differentiation, apoptosis, migration and invasion in several types of tumors, but its role in cervical carcinoma remains poorly understood. In this study, we showed that BMX expression exhibits a gradually increasing trend from normal cervical tissue to cervical cancer in situ and then to invasive cervical cancer tissue. Through BMX-IN-1, a potent and irreversible BMX kinase inhibitor, inhibited the expression of BMX, the cell proliferation was significantly decreased...
July 25, 2017: Oncotarget
Alyssa L DeMarco, Craig A Good, Dennis D Chimich, Jeff A Bakal, Gunter P Siegmund
Helmet manufacturers recommend replacing a bicycle helmet after an impact or after anywhere from 2 to 10 years of use. The goal of this study was to quantify the effect of helmet age on peak headform acceleration during impact attenuation testing of field-used bicycle helmets. Helmets were acquired by donation from consumers and retail stores, and were included in the study if they were free of impact-related damage, had a legible manufacture date label, and were certified to at least one helmet standard. Helmets (n = 770) spanning 0-26 years old were drop tested to measure peak linear headform acceleration during impacts to the right and left front regions of the helmets at two impact speeds (3...
May 1, 2017: Annals of Biomedical Engineering
Donghui Zhou, Maya Z Springer, David Xu, Degang Liu, Andy Hudmon, Kay F Macleod, Samy O Meroueh
Triple-negative breast cancers (TNBCs) lack the signature targets of other breast tumors, such as HER2, estrogen receptor, and progesterone receptor. These aggressive basal-like tumors are driven by a complex array of signaling pathways that are activated by multiple driver mutations. Here we report the discovery of 6 (KIN-281), a small molecule that inhibits multiple kinases including maternal leucine zipper kinase (MELK) and the non-receptor tyrosine kinase bone marrow X-linked (BMX) with single-digit micromolar IC50 s...
June 15, 2017: Bioorganic & Medicinal Chemistry
X Fang, Y Hu, Y Wang, S Liu, F Wang, X L Chen
Objective: To investigate the role of bone marrow tyrosine kinase on chromosome X (BMX) in the production of tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β) from mouse mononuclear-macrophages induced by endotoxin/lipopolysaccharide (LPS) and its related mechanism. Methods: Mouse mononuclear-macrophages RAW264.7 were inoculated in 6-well plates and routinely cultured for the following experiments. (1) Cells were collected and divided into blank control group, LPS control group, and 75, 750, 7 500, 75 000 nmol/L BMX-IN-1 pretreatment groups according to the random number table, with 8 wells in each group...
April 20, 2017: Zhonghua Shao Shang za Zhi, Zhonghua Shaoshang Zazhi, Chinese Journal of Burns
Ye Wang, Jufeng Xia, Zhaoyuan Fang, Fei Li, Duo Li, Zuoyun Wang, Yan Feng, Jian Zhang, Haiquan Chen, Hongbin Ji, Hongyan Liu
The non-receptor tyrosine kinase BMX has been reported in several solid tumors. However, the alternative splicing of BMX and its clinical relevance in lung cancer remain to be elucidated. Exon1.0 array was used to identify a novel alternative splicing of BMX, BMXΔN, which was confirmed by rapid amplification of cDNA ends and reverse transcription-polymerase chain reaction. BMXΔN, resulting from exon skipping with excluding exon 1 to exon 8 of BMX gene, was found in 12% human lung adenocarcinoma specimens...
May 16, 2017: Oncotarget
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