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Nikita Nirwan, Fouzia Siraj, Divya Vohora
OBJECTIVE: Currently, lacosamide (LCM) is not approved for use in status epilepticus (SE) but several shreds of evidence are available to support its use. The present study was, therefore, undertaken to evaluate the effect of LCM on pilocarpine (PILO) induced SE and neurodegeneration in C57BL/6 mice and to ascertain the involvement of CRMP-2 in mediating above effect. METHODS: Pilocarpine-induced SE model was developed to explore the effect of LCM 20, 40 and 80 mg/kg in mice...
June 18, 2018: Epilepsy Research
Melina Mottin, Joyce V V B Borba, Rodolpho C Braga, Pedro H M Torres, Matheus C Martini, Jose Luiz Proenca-Modena, Carla C Judice, Fabio T M Costa, Sean Ekins, Alexander L Perryman, Carolina Horta Andrade
Despite the recent outbreak of Zika virus (ZIKV), there are still no approved treatments, and early-stage compounds are probably many years away from approval. A comprehensive A-Z review of the recent advances in ZIKV drug discovery efforts is presented, highlighting drug repositioning and computationally guided compounds, including discovered viral and host cell inhibitors. Promising ZIKV molecular targets are also described and discussed, as well as targets belonging to the host cell, as new opportunities for ZIKV drug discovery...
June 20, 2018: Drug Discovery Today
Anton Buzdin, Maxim Sorokin, Andrew Garazha, Marina Sekacheva, Ella Kim, Nikolay Zhukov, Ye Wang, Xinmin Li, Souvik Kar, Christian Hartmann, Amir Samii, Alf Giese, Nicolas Borisov
Anticancer target drugs (ATDs) specifically bind and inhibit molecular targets that play important roles in cancer development and progression, being deeply implicated in intracellular signaling pathways. To date, hundreds of different ATDs were approved for clinical use in the different countries. Compared to previous chemotherapy treatments, ATDs often demonstrate reduced side effects and increased efficiency, but also have higher costs. However, the efficiency of ATDs for the advanced stage tumors is still insufficient...
June 20, 2018: Seminars in Cancer Biology
Michelle C Kegler, Erin Lebow-Skelley, Jaimie Lea, Adrienne M Lefevre, Pam Diggs, Sally Herndon, Regine Haardörfer
PURPOSE AND OBJECTIVES: In 2016, the US Department of Housing and Urban Development (HUD) issued a new rule requiring smoke-free policies in conventional public housing by July 2018 (HUD, 2016). This process evaluation describes the policy development experiences of conventional and nonconventional public housing authorities (PHAs) in North Carolina and Georgia that had established smoke-free policies before the HUD rule. INTERVENTION APPROACH: HUD began to issue guidance that encouraged smoke-free policies in public housing in 2009, and most early adopters were outside of the Southeast...
June 21, 2018: Preventing Chronic Disease
Dalia Mohamed, Maha Kamal
A sensitive HPLC-MS/MS method was established for the quantification of ceftriaxone sodium (CFT) and lidocaine HCl (LDC) in human plasma utilizing cefixime (CFX) and tadalafil (TDA) as internal standards. The analytes were extracted from human plasma by protein precipitation using acetonitrile. Chromatographic separation was performed on Kinetex C18 (50.0 x 4.6 mm, 5 μm particle size) column with methanol: 0.01 M ammonium acetate pH 6.4 (70: 30, v/v) as mobile phase. Multiple reaction monitoring involving the transitions 555...
June 22, 2018: Biomedical Chromatography: BMC
Carlson Alexander, A Nithyakumar, M Wilson Bosco Paul, N Arockia Samy
The synthesis of the platinum(II) complexes, [Pt(AIP)(bpy)](PF6 )2 (1) and [Pt(PIP)(phen)](PF6 )2 (2), of anthracene- and pyrene-conjugated imidazophenanthroline ligands and their in vitro cytotoxicity toward the fibroblast cells and the HeLa cell lines are reported. MTT assay demonstrates their cytotoxicity against the HeLa cell lines with the IC50 values of 1.35 and 1.56 µM, respectively, and the cytotoxicity profiles indicate that the HeLa cell lines show more activity than the fibroblast cells. Trypan blue assay highlights significant damage on the HeLa cell lines with a pronounced reduction on their clonogenicity...
July 2018: Journal of Biological Inorganic Chemistry: JBIC
Teck Wei Tan, Rajesh Nair, Sanad Saad, Ramesh Thurairaja, Muhammad Shamim Khan
PURPOSE: We report the perioperative outcomes and complications after transition from extracorporeal urinary diversion (ECUD) to intracorporeal urinary diversion (ICUD) following robot-assisted radical cystectomy (RARC). METHODS: Analysis of data from a prospectively maintained institutional review board-approved database of 180 patients treated with cystectomy at our institution from April 2015 to October 2017 was performed. 127 patients underwent RARC and received an ileal conduit...
June 22, 2018: World Journal of Urology
Aditya Kulkarni, Paola Caporali, Atul Dolas, Soniya Johny, Sandeep Goyal, Jessica Dragotto, Alberto Macone, Ramesh Jayaraman, Maria Teresa Fiorenza
Niemann-Pick Type C1 disorder (NPC) is a rare lysosomal storage disease characterized by the accumulation of cholesterol in lysosomes. NPC has no FDA approved treatments yet, however 2-hydroxypropyl-β-cyclodextrin (HPβCD) has shown efficacy for treating the disease in both mouse and feline NPC models and is currently being investigated in late stage clinical trials. Despite promising results, therapeutic use of HPβCD is limited by the need for high doses, ototoxicity and intrathecal administration. These limitations can be attributed to its poor pharmacokinetic profile...
June 22, 2018: Scientific Reports
Sebastian Rauer, Lidia Stork, Horst Urbach, Angeliki Stathi, Anna Marx, Patrick Süß, Marco Prinz, Wolfgang Brück, Imke Metz
OBJECTIVE: To report on 2 women with multiple sclerosis (MS) who developed severe neurologic deterioration and a drug reaction with eosinophilia and systemic symptoms (DRESS) after treatment with 2 and 4 subcutaneous injections of daclizumab, respectively. METHODS: This report includes clinical, MRI, and histopathologic data. RESULTS: Daclizumab is a humanized monoclonal antibody that binds the interleukin-2 receptor. It was approved for the treatment of relapsing MS...
June 22, 2018: Neurology
Salma Ladhani, Brianna Empringham, Kuan-Wen Wang, Carol Portwine, Laura Banfield, Russell J de Souza, Lehana Thabane, M Constantine Samaan
INTRODUCTION: Acute lymphoblastic leukaemia is the most common paediatric cancer. Survivors of childhood acute lymphoblastic leukaemia (SALL) are at risk of obesity and related cardiometabolic diseases including type 2 diabetes, hypertension, stroke and cardiovascular events. Therefore, it is important to address obesity in this population as this may help mitigate future cardiometabolic comorbidities. In this systematic review, we aim to assess current treatment strategies including lifestyle interventions, pharmacotherapy and bariatric surgery to manage overweight and obesity in SALL...
June 22, 2018: BMJ Open
Harsha Shanthanna, James Paul, Peter Lovrics, P J Devereaux, Mohit Bhandari, Lehana Thabane
INTRODUCTION: There has been an exponential increase in the number of ambulatory surgeries (AS). Pain and postoperative nausea vomiting (PONV) affects the recovery, discharge and overall satisfaction of patients having AS. Opioids remain the primary modality for moderate to severe pain. Since there is no perfect opioid, physicians should ideally use the opioid that optimally balances benefits and risks. Present decisions on the choice between morphine (M) and hydromorphone (HM) are based on individual experience and observation...
June 22, 2018: BMJ Open
Daniel I McIsaac, Chelsey Saunders, Emily Hladkowicz, Gregory L Bryson, Alan J Forster, Sylvain Gagne, Allen Huang, Manoj Lalu, Luke T Lavallee, Husein Moloo, Julie Nantel, Barbara Power, Celena Scheede-Bergdahl, Monica Taljaard, Carl van Walraven, Colin J L McCartney
INTRODUCTION: Exercise prehabilitation may improve outcomes after surgery. Frailty is a key predictor of adverse postoperative outcomes in older people; the multidimensional nature of frailty makes this a population who may derive substantial benefit from exercise prehabilitation. The objective of this trial is to test the efficacy of exercise prehabilitation to improve postoperative functional outcomes for people living with frailty having cancer surgery with curative intent. METHODS AND ANALYSIS: We will conduct a single-centre, parallel-arm randomised controlled trial of home-based exercise prehabilitation versus standard care among consenting patients >60 years having elective cancer surgery (intra-abdominal and intrathoracic) and who are frail (Clinical Frailty Scale >4<u>)</u>...
June 22, 2018: BMJ Open
Jian-Wei Cui, Yinyan Xu, Yibo Wang, Yan-Xia Gao, Shigong Guo, Meng Wang, Xin Lu, Shiyuan Yu, Yong Ma, Ding Yuan, Lu Che, Pei Sun, Xuezhong Yu, Huadong Zhu, Yi Li
INTRODUCTION: Paraquat (PQ) is a widely used herbicide which is inexpensive and easily accessible for people in rural areas. A small amount of PQ ingestion could be lethal, yet currently, the optimal treatment is still controversial. Extracorporeal therapies (ECTR) have been practised in PQ poisoning management, though limited evidence could be obtained to suggest its superiority over conservative therapy. Haemodialysis (HD) and haemoperfusion (HP) are most commonly used, while some institutions also choose HP-HD concurrent therapy...
June 22, 2018: BMJ Open
Thomas M Withers, Louise Croft, Victoria L Goosey-Tolfrey, David W Dunstan, Christof A Leicht, Daniel P Bailey
INTRODUCTION: Sedentary behaviour is a distinct risk factor for cardiovascular disease (CVD) and could partly explain the increased prevalence of CVD in people with spinal cord injury (SCI). Interrupting prolonged sitting periods with regular short bouts of walking acutely suppresses postprandial glucose and lipids in able-bodied individuals. However, the acute CVD risk marker response to breaking up prolonged sedentary time in people with SCI has not been investigated. METHODS AND ANALYSIS: A randomised two-condition laboratory crossover trial will compare: (1) breaking up prolonged sedentary time with 2 min moderate-intensity arm-crank activity every 20 min, with (2) uninterrupted prolonged sedentary time (control) in people with SCI...
June 22, 2018: BMJ Open
Katherine A Benfer, Iona Novak, Catherine Morgan, Koa Whittingham, Naila Zaman Khan, Robert S Ware, Kristie L Bell, Sasaka Bandaranayake, Alison Salt, Asis Kumar Ghosh, Anjan Bhattacharya, Sandip Samanta, Golam Moula, Dilip Bose, Santanu Tripathi, Roslyn N Boyd
INTRODUCTION: Cerebral palsy (CP) is the most common childhood physical disability, with 80% estimated to be in low-middle-income countries. This study aims to (1) determine the accuracy of General Movements (GMs)/Hammersmith Infant Neurological Examination (HINE) for detecting CP at 18 months corrected age (CA); (2) determine the effectiveness of a community-based parent-delivered early intervention for infants at high risk of CP in West Bengal, India (Learning through Everyday Activities with Parents for infants with CP; LEAP-CP)...
June 22, 2018: BMJ Open
Guohua Zheng, Yuhui Zheng, Zhenyu Xiong, Bingzhao Ye, Jing Tao, Lidian Chen
INTRODUCTION: Poststroke cognitive impairment is one of the most common complications in stroke survivors, and >65% of these patients suffer from cognitive impairment at 12 months following onset, which strongly affects the rehabilitation of their motor function and quality of life. Therefore, it is important to improve the cognitive ability of stroke survivors. As an important component of traditional Chinese Qigong exercises, characterised by the coordination of mind and body with a low exercise intensity, Baduanjin has the potential benefit of improving cognitive ability for patients who had a stroke with cognitive impairment...
June 22, 2018: BMJ Open
Yasuo Okumura, Ikuo Fukuda, Mashio Nakamura, Norikazu Yamada, Morimasa Takayama, Hideaki Maeda, Takeshi Yamashita, Takanori Ikeda, Makoto Mo, Tsutomu Yamazaki, Atsushi Hirayama
INTRODUCTION: Rivaroxaban, a factor Xa inhibitor used as a direct oral anticoagulant, is beneficial over warfarin in terms of food-drug interactions and the need for therapeutic monitoring in patients with acute venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism. Because there is little data regarding VTE treatment in Japan, a real-world survey of Japanese patients being treated with rivaroxaban for VTE is needed. METHODS AND ANALYSIS: The Japanese Registry of Rivaroxaban Effectiveness & Safety for the Prevention of Recurrence in Patients with Deep Vein Thrombosis and Pulmonary Embolism has been established to investigate the clinical outcomes of rivaroxaban for the initial treatment and prevention of symptomatic recurrent VTE in Japanese patients with acute symptomatic/asymptomatic VTE...
June 22, 2018: BMJ Open
Andrea C Chaikovsky, Julien Sage
Inhibitors of the cyclin-dependent kinases 4 and 6 (CDK4/6) were originally designed to block proliferation and cell cycle progression of cancer cells in which the activity of these kinases is dysregulated. CDK4/6 inhibitors have already been FDA-approved for the treatment of estrogen receptor (ER)-positive breast cancer and are being tested in numerous other cancer types. However, several recent studies have identified novel effects of CDK4/6 inhibitors on tumor growth, most notably an indirect effect resulting from the activation of immune surveillance...
June 22, 2018: Molecular Cancer Research: MCR
Kathryn Millar, Suha Patel, Meghan Munson, Linda Vesel, Shalini Subbiah, Rachel M Jones, Sarah Little, Aris T Papageorghiou, Jose Villar, Mary Nell Wegner, Nick Pearson, Faith Muigai, Catherine Ongeti, Ana Langer
BACKGROUND: The burden of preterm birth, fetal growth impairment, and associated neonatal deaths disproportionately falls on low- and middle-income countries where modern obstetric tools are not available to date pregnancies and monitor fetal growth accurately. The INTERGROWTH-21st gestational dating, fetal growth monitoring, and newborn size at birth standards make this possible. OBJECTIVE: To scale up the INTERGROWTH-21st standards, it is essential to assess the feasibility and acceptability of their implementation and their effect on clinical decision-making in a low-resource clinical setting...
June 22, 2018: JMIR Research Protocols
John Paul Clancy, Calvin U Cotton, Scott H Donaldson, George M Solomon, Donald R VanDevanter, Michael P Boyle, Martina Gentzsch, Jerry A Nick, Beate Illek, John C Wallenburg, Eric J Sorscher, Margarida D Amaral, Jeffrey M Beekman, Anjaparavanda P Naren, Robert J Bridges, Philip J Thomas, Garry Cutting, Steven Rowe, Anthony G Durmowicz, Martin Mense, Kris D Boeck, William Skach, Christopher Penland, Elizabeth Joseloff, Hermann Bihler, John Mahoney, Drucy Borowitz, Katherine L Tuggle
BACKGROUND: New drugs that improve the function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein with discreet disease-causing variants have been successfully developed for cystic fibrosis (CF) patients. Preclinical model systems have played a critical role in this process, and have the potential to inform researchers and CF healthcare providers regarding the nature of defects in rare CFTR variants, and to potentially support use of modulator therapies in new populations...
June 19, 2018: Journal of Cystic Fibrosis: Official Journal of the European Cystic Fibrosis Society
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