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Brinda Emu, Jeffrey Fessel, Shannon Schrader, Princy Kumar, Gary Richmond, Sandra Win, Steven Weinheimer, Christian Marsolais, Stanley Lewis
BACKGROUND: Ibalizumab, a humanized IgG4 monoclonal antibody, blocks the entry of human immunodeficiency virus type 1 (HIV-1) by noncompetitive binding to CD4. METHODS: In this single-group, open-label, phase 3 study, we enrolled 40 adults with multidrug-resistant (MDR) HIV-1 infection in whom multiple antiretroviral therapies had failed. All the patients had a viral load of more than 1000 copies of HIV-1 RNA per milliliter. After a 7-day control period in which patients continued to receive their current therapy, a loading dose of 2000 mg of ibalizumab was infused; the viral load was quantified 7 days later...
August 16, 2018: New England Journal of Medicine
Joanne L Hardstaff, Helen E Clough, Vittoria Lutje, K Marie McIntyre, John P Harris, Paul Garner, Sarah J O'Brien
Norovirus (NoV) is the commonest cause of gastrointestinal disease in the United Kingdom and in many developed countries, causing diarrhea and vomiting in millions of cases worldwide annually. Transmission is most often mediated from person to person. NoV infection has, however, additionally been associated with the consumption of food, either through the consumption of food contaminated at source such as seafood, berries, and salad, or as a consequence of the foodstuff being contaminated in some way by a food handler during processing or serving...
August 15, 2018: Foodborne Pathogens and Disease
Fernanda P Eduardo, Leticia Mello Bezinelli, Marcella Gobbi, Flavia C P Rosin, Danielle L C Carvalho, Mariana Henriques Ferreira, Cinthya Correa da Silva, Nelson Hamerschlak, Luciana Corrêa
Busulfan is a major component of chemotherapy conditioning in hematopoietic cell transplantation (HCT). This alkylating agent is highly toxic at myeloablative doses, exposing HCT patients to risks of mortality. Non-myeloablative (NMA) and reduced-intensity conditioning (RIC) using busulfan have shown impaired toxicity. However, the toxicity of NMA/RIC in the digestive tract is poorly described. This study aimed to characterize the mucositis in the oral cavity (OM), oropharynx/esophagus, and gastrointestinal tract derived from conditionings with myeloablative and non-myeloablative doses of busulfan...
August 14, 2018: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
Anna Maikova, Konstantin Severinov, Olga Soutourina
Over the last decades the enteric bacterium Clostridium difficile (novel name Clostridioides difficile ) - has emerged as an important human nosocomial pathogen. It is a leading cause of hospital-acquired diarrhea and represents a major challenge for healthcare providers. Many aspects of C. difficile pathogenesis and its evolution remain poorly understood. Efficient defense systems against phages and other genetic elements could have contributed to the success of this enteropathogen in the phage-rich gut communities...
2018: Frontiers in Microbiology
Wichuda Phothichaisri, Puey Ounjai, Tanaporn Phetruen, Tavan Janvilisri, Pongsak Khunrae, Sombat Singhakaew, Piyada Wangroongsarb, Surang Chankhamhaengdecha
Clostridium difficile is recognized as a problematic pathogen, causing severe enteric diseases including antibiotic-associated diarrhea and pseudomembranous colitis. The emergence of antibiotic resistant C. difficile has driven a search for alternative anti-infection modalities. A promising strategy for controlling bacterial infection includes the use of bacteriophages and their gene products. Currently, knowledge of phages active against C. difficile is still relatively limited by the fact that the isolation of phages for this organism is a technically demanding method since bacterial host themselves are difficult to culture...
2018: Frontiers in Microbiology
George Oche Ambrose, Olanrewaju John Afees, Nwufoh Chika Nwamaka, Nzikahyel Simon, Adebo Adeola Oluwaseun, Tosin Soyinka, Alakanse Suleiman Oluwaseun, Seyi Bankole
The life-threatening sides effect of the current EGFR mutant inhibitors (drugs) such as the eruption of rash which can be seen on the face, chest, back and even the trunk, diarrhea, nausea, vomiting, anorexia and stomatitis, necessitates the discovery of new potent and safe compounds as a chemo-therapeutic measure against lung cancer. Approximately about 10% of patients with Non-small cell lung cancer (NSCLC) in the US and about 35% in East Asia have tumor associated EGFR. These mutations occur within EGFR exon 18-21, which encodes a portion of the EGFR kinase domain and enables researchers to identify compounds that only recognizes and binds to the cancer cells...
2018: Bioinformation
Stephanie Lheureux, Anna V Tinker, Blaise A Clarke, Prafull Ghatage, Stephen Welch, Johanne I Weberpals, Neesha C Dhani, Marcus O Butler, Katia Tonkin, Qian Tan, David S P Tan, Kelly Brooks, Janelle Ramsahai, Lisa Wang, Nhu-An Pham, Patricia A Shaw, Ming-Sound Tsao, Swati Garg, Tracy L Stockley, Amit M Oza
PURPOSE: Patients with recurrent ovarian clear cell carcinoma (OCCC) have limited effective options due to chemo-resistance. A phase II study was designed to assess the activity of ENMD-2076, an oral multi-target kinase selective against Aurora-A and VEGFR. EXPERIMENTAL DESIGN: This multi-center Phase II study included patients with recurrent OCCC who received prior platinum-based chemotherapy. Primary endpoints were objective response and 6-month progression free survival (PFS) rates...
August 14, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Nannan Gao, Tengyue Zhang, Jiadong Ji, Kai-Feng Xu, Xinlun Tian
BACKGROUND: Lymphangioleiomyomatosis (LAM) is a rare lung disease and the mammalian target of the rapamycin (mTOR) inhibitors has been used as an effective therapy. Here we conducted a systematic review and meta-analysis with the aims to quantify the efficacy and safety of mTOR inhibitors in LAM patients. METHODS: The following databases were searched for clinical trials regarding LAM patients treated with mTOR inhibitors until December 2017: Pubmed, Embase, Cochrane Library and OVID medicine...
August 14, 2018: Orphanet Journal of Rare Diseases
Damien Costa, Romy Razakandrainibe, Marc Sautour, Stéphane Valot, Louise Basmaciyan, Gilles Gargala, Denis Lemeteil
Cryptosporidiosis is a common disease in children and immunodeficient individuals. In 2006, a national network was set up on the surveillance of human cryptosporidiosis in France. Since January 2015, the 41 tertiary care hospitals and the 3 private laboratories of the French National Network on the surveillance of human cryptosporidiosis have been able to declare confirmed cases of cryptosporidiosis online. Between 2015 and 2017, 210 cases of cryptosporidiosis were declared in immunodeficient patients in France; Cryptosporidium parvum and Cryptosporidium hominis represented 66% and 22% of cases, respectively...
August 11, 2018: Experimental Parasitology
Quentin Vicens, Estefanía Mondragón, Francis E Reyes, Philip Coish, Paul Aristoff, Judd Berman, Harpreet Kaur, Kevin W Kells, Phil Wickens, Jeffrey Wilson, Robert C Gadwood, Heinrich J Schostarez, Robert K Suto, Kenneth F Blount, Robert T Batey
The flavin mononucleotide (FMN) riboswitch is an emerging target for the development of novel RNA-targeting antibiotics. We previously discovered an FMN derivative -5FDQD- that protects mice against diarrhea-causing Clostridium difficile bacteria. Here, we present the structure-based drug design strategy that led to the discovery of this fluoro-phenyl derivative with antibacterial properties. This approach involved the following stages: (1) structural analysis of all available free and bound FMN riboswitch structures; (2) design, synthesis and purification of derivatives; (3) in vitro testing for productive binding using two chemical probing methods; (4) in vitro transcription termination assays; (5) resolution of the crystal structures of the FMN riboswitch in complex with the most mature candidates...
August 14, 2018: ACS Chemical Biology
Ouidad Zehou, Claire Leibler, Jean-Philippe Arnault, Johnny Sayegh, Henri Montaudié, Philippe Rémy, Denis Glotz, Carole Cordonnier, Ludovic Martin, Céleste Lebbé
Immune checkpoint inhibitors are new therapeutic options for metastatic melanoma, but little data is available in organ transplant recipient populations. Six French patients, 3 men and 3 women, mean age 66 years (range 44-74), all kidney transplant recipients, received ipilimumab (CTLA-4 inhibitor) for metastatic melanoma. At diagnosis of advanced melanoma, immunosuppressive therapy had been minimized in all but one. Adverse effects included one case of grade 1 diarrhea and one grade 1 pruritus. One patient had acute T-cell-mediated rejection confirmed by histology, after the first injection of ipilimumab...
August 14, 2018: American Journal of Transplantation
Roselin Valle-Cabrera, Yudexi Mendoza-Rodríguez, Maytee Robaina-García, Javier Ballesteros, Juan Rafael Cordero-Jiménez, Nadia B Espinosa-Rodríguez, Yenia Sotolongo-Garcia, Bianca Lauria-Horner
PURPOSE: The aim of this study was to assess the efficacy and safety of sertraline compared with placebo in a good clinical practice trial conducted with major depressive disorder patients naive to selective serotonin reuptake inhibitors. METHODS: This was a 10-week randomized, multicenter, placebo-controlled, double blind, superiority trial. Adult patients diagnosed with major depressive disorder (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria), total score of 19 to 36 in the 17-item Hamilton Depression Rating Scale (HAMD-17), were randomly allocated to sertraline (n = 39) or placebo (n = 38)...
August 14, 2018: Journal of Clinical Psychopharmacology
Kimmie Ng, Andrew Hendifar, Alexander Starodub, Jorge Chaves, Yingsi Yang, Brian Koh, David Barbie, William C Hahn, Charles S Fuchs
Purpose Preclinical evidence suggests the importance of Janus activating kinase (JAK) and TANK-binding kinase 1 (TBK1) in pancreatic ductal adenocarcinoma (PDAC). We evaluated the safety and efficacy of momelotinib (MMB), a JAK1/2 inhibitor with additional activity against TBK1, plus albumin-bound paclitaxel + gemcitabine (nab-P + G), in patients with previously untreated metastatic PDAC. Experimental Design Patients were enrolled into five cohorts of increasing doses of MMB between 100 and 200 mg administered once or twice daily in combination with nab-P + G in 28-day cycles to determine maximum tolerated dose (MTD)...
July 30, 2018: Investigational New Drugs
Christopher Troeger, Ibrahim A Khalil, Puja C Rao, Shujin Cao, Brigette F Blacker, Tahmeed Ahmed, George Armah, Julie E Bines, Thomas G Brewer, Danny V Colombara, Gagandeep Kang, Beth D Kirkpatrick, Carl D Kirkwood, Jason M Mwenda, Umesh D Parashar, William A Petri, Mark S Riddle, A Duncan Steele, Robert L Thompson, Judd L Walson, John W Sanders, Ali H Mokdad, Christopher J L Murray, Simon I Hay, Robert C Reiner
Importance: Rotavirus infection is the global leading cause of diarrhea-associated morbidity and mortality among children younger than 5 years. Objectives: To examine the extent of rotavirus infection among children younger than 5 years by country and the number of deaths averted because of the rotavirus vaccine. Design, Setting, and Participants: This report builds on findings from the Global Burden of Disease Study 2016, a cross-sectional study that measured diarrheal diseases and their etiologic agents...
August 13, 2018: JAMA Pediatrics
Linger Liu, Zhenghua Fei, Mengfeng Chen, Lihao Zhao, Huafang Su, Dianna Gu, Baochai Lin, Xiaona Cai, Lihuai Lu, Mengdan Gao, Xuxue Ye, Xiance Jin, Congying Xie
BACKGROUND: In the era of intensity-modulated radiotherapy (IMRT), the role of additional concurrent chemotherapy (CC) to radiotherapy (RT) after induction chemotherapy (IC) compared to IC followed by RT alone remains unclear for stage II-IVB nasopharyngeal carcinoma (NPC) patients. The aim of this study was to evaluate the efficacy and toxicities of IC/RT and IC/CCRT in the treatment of NPC with volumetric modulated arc therapy (VMAT). METHODS: From January 2012 to March 2016, a total of 217 NPC patients were retrospectively assessed...
August 13, 2018: Radiation Oncology
Hee Jung Jeon, Hahn-Ey Lee, Jaeseok Yang
BACKGROUND: Few post-marketing surveillance studies have examined the safety and efficacy of Rapamune® (Sirolimus) in Asian countries. This study aimed to better understand safety and efficacy of Rapamune for kidney transplant recipients in the routine clinical practice setting in Korea. METHODS: This was an open-label, non-comparative, observational, prospective, multi-center, post-marketing surveillance study conducted at 15 Korean transplant centers between 31 August 2009 and 24 September 2015...
August 13, 2018: BMC Nephrology
Robert A Kloner, Coleman Gross, Jinwei Yuan, Ansgar Conrad, Pablo E Pergola
INTRODUCTION: Hyperkalemia (potassium >5.0 mEq/L) affects heart failure patients with renal disease regardless of the use of renin-angiotensin-aldosterone system inhibitors (RAASi). The open-label TOURMALINE study showed that patiromer, a sodium-free, nonabsorbed potassium binder, lowers serum potassium of hyperkalemic patients similarly when given with or without food; unlike prior studies, patients were not required to be taking RAASi. We conducted post hoc analyses to provide the first report of patiromer in patients not taking RAASi...
August 14, 2018: Journal of Cardiovascular Pharmacology and Therapeutics
Gianluca Ianiro, Gianenrico Rizzatti, Manuel Plomer, Loris Lopetuso, Franco Scaldaferri, Francesco Franceschi, Giovanni Cammarota, Antonio Gasbarrini
Acute diarrhea is a burdensome disease with potentially harmful consequences, especially in childhood. Despite its large use in clinical practice, the efficacy of the probiotic Bacillus clausii in treating acute childhood diarrhea remains unclear. Our objective was to systematically review the efficacy of Bacillus clausii in the treatment of acute childhood diarrhea. The following electronic databases were systematically searched up to October 2017: MEDLINE (via PubMed/OVID), EMBASE (via OVID), Cochrane Central Database of Controlled Trials (via CENTRAL), Google Scholar, and ClinicalTrials...
August 12, 2018: Nutrients
Zhichao Xu, Yun Zhang, Lang Gong, Licheng Huang, Ying Lin, Jianru Qin, Yunping Du, Qingfeng Zhou, Chunyi Xue, Yongchang Cao
Porcine enteric alphacoronavirus (PEAV) was first discovered in China in February 2017, and the origin and virulence of this novel porcine coronavirus were not fully characterized. Here, we isolated a strain of PEAV, named GDS04 that is identified by immunofluorescence and typical crown-shaped particles observed with electron microscopy. Genomic analysis reveals that PEAV GDS04 shares a close relationship with SADS-CoV and SeACoV. Furthermore, newborn piglets orally challenged with PEAV GDS04 developed typical clinical symptoms as watery diarrhea in neonatal piglets...
August 13, 2018: Transboundary and Emerging Diseases
Aravind Shekar, Shylaja Ramlal, Joseph Kingston Jeyabalaji, Murali Harishchandra Sripathy
Ruminants are the major reservoirs of Escherichia coli O157:H7 and its fecal shedding mainly act as a source of entry of this pathogen into the human food chain. In humans, E. coli O157:H7 infection causes diarrhea, hemorrhagic colitis and hemolytic uremic syndrome. Intimate adherence of E. coli O157:H7 is mediated by Translocated intimin receptor (Tir) to which intimin binds in the host cell. Since E. coli O157:H7 colonizes intestinal epithelium, the mucosal vaccine has a potential to prevent its colonization...
August 10, 2018: International Immunopharmacology
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