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First-in-human clinical studies

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https://www.readbyqxmd.com/read/28346849/clostridium-perfringens-type-a-isolates-of-animal-origin-with-decreased-susceptibility-to-metronidazole-show-extensive-genetic-diversity
#1
Sergio Álvarez-Pérez, José L Blanco, Marta E García
Metronidazole is a first-line drug for the treatment of human infections caused by anaerobic bacteria. Although most Clostridium perfringens isolates are susceptible to metronidazole, a number of strains with decreased susceptibility have been obtained in clinical and environmental surveys. However, little is known yet about the toxinotype and genetic diversity of metronidazole-resistant C. perfringens strains. We tested for susceptibility to metronidazole and assessed the toxigenic status and amplified fragment length polymorphism (AFLP) diversity of a collection of 80 C...
March 27, 2017: Microbial Drug Resistance: MDR: Mechanisms, Epidemiology, and Disease
https://www.readbyqxmd.com/read/28346848/cardiovascular-protective-effects-and-clinical-applications-of-resveratrol
#2
Sanghyun Cho, Kyung Namkoong, Minji Shin, Jueun Park, Eunyeong Yang, Jinsoo Ihm, Vu Thi Thu, Hyoung Kyu Kim, Jin Han
Resveratrol is a naturally occurring phenol that is generated by plant species following injury or attack by bacterial and fungal pathogens. This compound was first described as the French Paradox in 1992. Later in 2003, resveratrol was reported to activate sirtuins in yeast cells. Recent experimental studies have found that resveratrol offers a variety of benefits that include both anticarcinogenic and anti-inflammatory effects in addition to the ability to reverse obesity, attenuate hyperglycemia and hyperinsulinemia, protect heart and endothelial function, and increase the life span...
March 27, 2017: Journal of Medicinal Food
https://www.readbyqxmd.com/read/28346597/association-of-risk-of-viremia-immunosuppression-serious-clinical-events-and-mortality-with-increasing-age-in-perinatally-human-immunodeficiency-virus-infected-youth
#3
Anne M Neilan, Brad Karalius, Kunjal Patel, Russell B Van Dyke, Mark J Abzug, Allison L Agwu, Paige L Williams, Murli Purswani, Deborah Kacanek, James M Oleske, Sandra K Burchett, Andrew Wiznia, Miriam Chernoff, George R Seage, Andrea L Ciaranello
Importance: As perinatally human immunodeficiency virus-infected youth (PHIVY) in the United States grow older and more treatment experienced, clinicians need updated information about the association of age, CD4 cell count, viral load (VL), and antiretroviral (ARV) drug use with risk of opportunistic infections, key clinical events, and mortality to understand patient risks and improve care. Objective: To examine the incidence or first occurrence during follow-up of key clinical events (including Centers for Disease Control and Prevention stage B [CDC-B] and stage C [CDC-C] events) and mortality among PHIVY stratified by age, CD4 cell count, and VL and ARV status...
March 27, 2017: JAMA Pediatrics
https://www.readbyqxmd.com/read/28346512/bacterial-and-viral-pathogen-spectra-of-acute-respiratory-infections-in-under-5-children-in-hospital-settings-in-dhaka-city
#4
Golam Sarower Bhuyan, Mohammad Amir Hossain, Suprovath Kumar Sarker, Asifuzzaman Rahat, Md Tarikul Islam, Tanjina Noor Haque, Noorjahan Begum, Syeda Kashfi Qadri, A K M Muraduzzaman, Nafisa Nawal Islam, Mohammad Sazzadul Islam, Nusrat Sultana, Manjur Hossain Khan Jony, Farhana Khanam, Golam Mowla, Abdul Matin, Firoza Begum, Tahmina Shirin, Dilruba Ahmed, Narayan Saha, Firdausi Qadri, Kaiissar Mannoor
The study aimed to examine for the first time the spectra of viral and bacterial pathogens along with the antibiotic susceptibility of the isolated bacteria in under-5 children with acute respiratory infections (ARIs) in hospital settings of Dhaka, Bangladesh. Nasal swabs were collected from 200 under-five children hospitalized with clinical signs of ARIs. Nasal swabs from 30 asymptomatic children were also collected. Screening of viral pathogens targeted ten respiratory viruses using RT-qPCR. Bacterial pathogens were identified by bacteriological culture methods and antimicrobial susceptibility of the isolates was determined following CLSI guidelines...
2017: PloS One
https://www.readbyqxmd.com/read/28345344/unravelling-and-quantifying-the-nmr-invisible-metabolites-interacting-with-human-serum-albumin-by-binding-competition-and-t2-relaxation-based-decomposition-analysis
#5
Ruben Barrilero, Noelia Ramirez, Joan Carles Vallvé, Delia Taverner, Rocío Fuertes, Núria Amigó, Xavier Correig
Quantitative profiling of low-molecular-weight metabolites (LMWM) by 1H-NMR is routinely used in high-throughput serum metabolomics. First, the protein background is attenuated using a T2 filter, then the LMWM signals are resolved by line-shape fitting. However, protein binding modifies the motional properties of LMWM and their signal partially attenuates with the T2 filter, along with the protein background. Consequently, the quantified LMWM signal does not reflect the total concentration in serum but the non-binding part...
March 27, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28344888/pre-emptive-and-therapeutic-adoptive-immunotherapy-for-nasopharyngeal-carcinoma-phenotype-and-effector-function-of-t-cells-impact-on-clinical-response
#6
Corey Smith, Victor Lee, Andrea Schuessler, Leone Beagley, Sweera Rehan, Janice Tsang, Vivian Li, Randal Tiu, David Smith, Michelle A Neller, Katherine K Matthews, Emma Gostick, David A Price, Jacqueline Burrows, Glen M Boyle, Daniel Chua, Benedict Panizza, Sandro V Porceddu, John Nicholls, Dora Kwong, Rajiv Khanna
Adoptive T cell therapy has emerged as a powerful strategy to treat human cancers especially haematological malignancies. Extension of these therapies to solid cancers remains a significant challenge especially in the context of defining immunological correlates of clinical responses. Here we describe results from a clinical study investigating autologous Epstein-Barr virus (EBV)-specific T cells generated using a novel AdE1-LMPpoly vector to treat patients with nasopharyngeal carcinoma (NPC) either pre-emptively in at-risk patients with no or minimal residual disease (N/MRD) or therapeutically in patients with active recurrent/metastatic disease (ARMD)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28343802/-the-effect-of-methylphenidate-on-appetite-and-weight
#7
R Bou Khalil, N Fares, Y Saliba, J Tamraz, S Richa
OBJECTIVES: To better delineate in the medical literature the effect of methylphenidate on weight and appetite. METHODS: A search on PubMed was carried out for articles published with no restrictions on language or year of publication using the terms: "methylphenidate"; "weight"; "appetite". RESULTS: Methylphenidate increases dopamine and noradrenaline in synapses because of its blockage of the transporters of these monoamines in the frontal cortex and insular lobe...
March 23, 2017: L'Encéphale
https://www.readbyqxmd.com/read/28343347/bioanalysis-of-farnesyl-pyrophosphate-in-human-plasma-by-high-performance-liquid-chromatography-coupled-to-triple-quadrupole-tandem-mass-spectrometry-and-hybrid-quadrupole-orbitrap-high-resolution-mass-spectrometry
#8
Hiroshi Sugimoto, Mie Iguchi, Fumihiro Jinno
The isoprenoids farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP) are pivotal intermediates for cholesterol homeostasis and cell signaling in the mevalonate pathway. We developed a sensitive and selective high-performance liquid chromatography tandem triple quadrupole mass spectrometry (LC-QQQ-MS) method for FPP in human plasma without the need for a derivatization process. We optimized the sample preparation procedure to extract FPP and (13)C5-FPP (as internal standard) from sample fluids using methanol...
March 25, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28342946/negait-a-new-parser-for-medical-text-simplification-using-morphological-sentential-and-double-negation
#9
Partha Mukherjee, Gondy Leroy, David Kauchak, Srinidhi Rajanarayanan, Damian Y Romero Diaz, Nicole P Yuan, T Gail Pritchard, Sonia Colina
Many different text features influence text readability and content comprehension. Negation is commonly suggested as one such feature, but few general-purpose tools exist to discover negation and studies of the impact of negation on text readability are rare. In this paper, we introduce a new negation parser (NegAIT) for detecting morphological, sentential, and double negation. We evaluated the parser using a human annotated gold standard containing 500 Wikipedia sentences and achieved 95%, 89% and 67% precision with 100%, 80%, and 67% recall, respectively...
March 22, 2017: Journal of Biomedical Informatics
https://www.readbyqxmd.com/read/28341377/lrp5-from-bedside-to-bench-to-bone
#10
Bart O Williams
A role for Low-density lipoprotein related receptor 5 (LRP5) in human bone was first established by the identification of genetic alterations that led to dramatic changes in human bone mass. Shortly thereafter, mutations that altered the function of the Sclerostin (SOST) gene were also associated with altered human bone mass. Subsequent studies of LRP5 and Sclerostin have provided important insights into the mechanisms by which these proteins regulate skeletal homeostasis. Sclerostin normally binds to LRP5 and the related LRP6 protein and prevents their activation by Wnt ligands...
March 21, 2017: Bone
https://www.readbyqxmd.com/read/28340145/human-abuse-potential-of-the-new-opioid-analgesic-molecule-nktr-181-compared-with-oxycodone
#11
Lynn Webster, Jack Henningfield, August R Buchhalter, Suresh Siddhanti, Lin Lu, Aleksandrs Odinecs, Carlo J Di Fonzo, Michael A Eldon
Objective.:  Evaluate the human abuse potential, pharmacokinetics, pharmacodynamics, and safety of NKTR-181, a novel mu-opioid agonist molecule, relative to oxycodone. Design.:  This randomized, single-center, double-blind, active- and placebo-controlled five-period crossover study enrolled healthy, adult, non-physically dependent recreational opioid users. Setting.:  Inpatient clinical research site. Subjects. : Forty-two randomized subjects (73...
March 10, 2017: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
https://www.readbyqxmd.com/read/28339648/three-dimensional-testicular-organoid-a-novel-tool-for-the-study-of-human-spermatogenesis-and-gonadotoxicity-in-vitro%C3%A2
#12
Samuel S Pendergraft, Hooman Sadri-Ardekani, Anthony Atala, Colin E Bishop
Existing methods for evaluating the potential gonadotoxicity of environmental agents and pharmaceutical compounds rely heavily on animal studies. The current gold standard in vivo functional assays in animals are limited in their human predictive capacity. In addition, existing human two-dimensional in vitro models of testicular toxicity do not accurately reflect the in vivo situation. A more reliable testicular in vitro model system is needed to better assess the gonadotoxic potential of drugs prior to progression into clinical trials...
February 17, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28339036/fgf7-fgfr2-signal-promotes-invasion-and-migration-in-human-gastric-cancer-through-upregulation-of-thrombospondin-1
#13
Tingting Huang, Lei Wang, Dian Liu, Piao Li, Huihua Xiong, Liang Zhuang, Li Sun, Xianglin Yuan, Hong Qiu
Fibroblast growth factor 7 (FGF7) is a mesenchyme-specific heparin-binding growth factor that binds FGF receptor 2 (FGFR2) to regulate numerous cellular and physiological processes. FGF7/FGFR2 signal is associated with gastric cancer progression. In the present study, we investigated the molecular mechanism by which FGF7/FGFR2 promotes invasion and migration in human gastric cancer. We first demonstrated that increased FGFR2 expression in human gastric cancer tissues was significantly associated with tumor depth and clinical stage in human gastric cancer tissues...
March 22, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28338421/harnessing-the-osteogenicity-of-in-vitro-stem-cell-derived-mineralized-extracellular-matrix-as-3d-biotemplate-to-guide-bone-regeneration
#14
Yoke Chin Chai, Johanna Bolander, Ioannis Papantoniou, Jennifer Patterson, Jef Vleugels, Jan Schrooten, Frank P Luyten
Advanced biomaterials that are capable of guiding robust bone regeneration are highly demanded for translational therapy of bone defects or bone augmentation in clinics. One of the strategic approaches is to produce tissue engineering (TE) constructs that mediate bone regeneration by recapitulating the natural bone formation or healing process. In this study, we aimed at producing devitalized mineralized carriers with augmented bone forming capacity via a modified culture protocol (i.e., culture conditions with high calcium and/or phosphate concentrations) that first promotes cell growth and, subsequently, mineralized extracellular matrix (ECM) deposition by human periosteum-derived osteoprogenitor cells (hPDCs) on additive manufactured three-dimensional (3D) porous titanium (Ti)-based scaffolds...
March 24, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28336967/the-gene-expression-profiles-in-response-to-102-traditional-chinese-medicine-tcm-components-a-general-template-for-research-on-tcms
#15
Chao Lv, Xueting Wu, Xia Wang, Juan Su, Huawu Zeng, Jing Zhao, Shan Lin, Runhui Liu, Honglin Li, Xuan Li, Weidong Zhang
Traditional Chinese medicines (TCMs) have important therapeutic value in long-term clinical practice. However, because TCMs contain diverse ingredients and have complex effects on the human body, the molecular mechanisms of TCMs are poorly understood. In this work, we determined the gene expression profiles of cells in response to TCM components to investigate TCM activities at the molecular and cellular levels. MCF7 cells were separately treated with 102 different molecules from TCMs, and their gene expression profiles were compared with the Connectivity Map (CMAP)...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28335666/control-of-dental-derived-induced-pluripotent-stem-cells-through-modified-surfaces-for-dental-application
#16
Hyunmin Choi, Kyu-Hyung Park, Ah-Reum Lee, Chin Hee Mun, Yong Dae Shin, Yong-Beom Park, Young-Bum Park
OBJECTIVE: The aim of this study is to investigate the behaviour of iPSc derived from dental stem cells in terms of initial adhesion, differentiation potential on differently surface-treated titanium disc. MATERIALS AND METHODS: iPSc derived from human gingival fibroblasts (hGFs) were established using 4-reprogramming factors transduction with Sendai virus. The hGF-iPSc established in this study exhibited the morphology and growth properties similar to human embryonic stem (ES) cells and expressed pluripotency makers...
March 23, 2017: Acta Odontologica Scandinavica
https://www.readbyqxmd.com/read/28334935/genome-wide-association-study-of-iron-traits-and-relation-to-diabetes-in-the-hispanic-community-health-study-study-of-latinos-hchs-sol-potential-genomic-intersection-of-iron-and-glucose-regulation
#17
Laura M Raffield, Tin Louie, Tamar Sofer, Deepti Jain, Eli Ipp, Kent D Taylor, George J Papanicolaou, Larissa Avilés-Santa, Leslie A Lange, Cathy C Laurie, Matthew P Conomos, Timothy A Thornton, Yii-Der Ida Chen, Qibin Qi, Scott Cotler, Bharat Thyagarajan, Neil Schneiderman, Jerome I Rotter, Alex P Reiner, Henry J Lin
Genetic variants contribute to normal variation of iron-related traits and may also cause clinical syndromes of iron deficiency or excess. Iron overload and deficiency can adversely affect human health. For example, elevated iron storage is associated with increased diabetes risk, although mechanisms are still being investigated. We conducted the first genome-wide association study (GWAS) of serum iron, total iron binding capacity (TIBC), transferrin saturation, and ferritin in a Hispanic/Latino cohort, the Hispanic Community Health Study/Study of Latinos (HCHS/SOL; >12,000 participants) and also assessed the generalization of previously known loci to this population...
March 7, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28334047/clinical-validation-of-chemotherapy-predictors-developed-on-global-microrna-expression-in-the-nci60-cell-line-panel-tested-in-ovarian-cancer
#18
Kira Philipsen Prahm, Claus Høgdall, Mona Aarenstrup Karlsen, Ib Jarle Christensen, Guy Wayne Novotny, Steen Knudsen, Anker Hansen, Peter Buhl Jensen, Thomas Jensen, Mansoor Raza Mirza, Anne Weng Ekmann-Gade, Lotte Nedergaard, Estrid Høgdall
OBJECTIVE: Ovarian cancer is the leading cause of death among gynecologic malignancies. This is partly due to a non-durable response to chemotherapy. Prediction of resistance to chemotherapy could be a key role in more personalized treatment. In the current study we aimed to examine if microRNA based predictors could predict resistance to chemotherapy in ovarian cancer, and to investigate if the predictors could be prognostic factors for progression free and overall survival. METHODS: Predictors of chemotherapy-resistance were developed based on correlation between miRNA expression and differences in measured growth inhibition in a variety of human cancer cell lines in the presence of Carboplatin, Paclitaxel and Docetaxel...
2017: PloS One
https://www.readbyqxmd.com/read/28333293/intra-individual-purifying-selection-on-mitochondrial-dna-variants-during-human-oogenesis
#19
Sara De Fanti, Saverio Vicario, Martin Lang, Domenico Simone, Cristina Magli, Donata Luiselli, Luca Gianaroli, Giovanni Romeo
Study Question: Does selection for mtDNA mutations occur in human oocytes? Summary Answer: We provide statistical evidence in favor of the existence of purifying selection for mtDNA mutations in human oocytes acting between the expulsion of the first and second polar bodies (PBs). What is Known Already: Several lines of evidence in Metazoa, including humans, indicate that variation within the germline of mitochondrial genomes is under purifying selection...
March 9, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28333245/euploidy-rates-in-donor-egg-cycles-significantly-differ-between-fertility-centers
#20
S Munné, M Alikani, L Ribustello, P Colls, Pedro A Martínez-Ortiz, D H McCulloh
STUDY QUESTION: Do external factors affect euploidy in egg donor cycles? SUMMARY ANSWER: The study demonstrates that during human assisted reproduction, embryonic chromosome abnormalities may be partly iatrogenic. WHAT IS KNOWN ALREADY: Chromosome abnormalities have been linked in the past to culture conditions such as temperature and Ph variations, as well as hormonal stimulation. Those reports were performed with older screening techniques (FISH), or ART methods no longer in use, and the subjects studied were not a homogeneous group...
March 2, 2017: Human Reproduction
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