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https://www.readbyqxmd.com/read/28346105/high-throughput-clonogenic-analysis-of-3d-cultured-patient-derived-cells-with-a-micropillar-and-microwell-chip
#1
Dong Woo Lee, Sang-Yun Lee, Lily Park, Mi-Sun Kang, Myoung-Hee Kim, Il Doh, Gyu Ha Ryu, Do-Hyun Nam
A high-throughput clonogenic assay with a micropillar-microwell chip platform is proposed by using the colony area of glioblastoma multiforme (GBM) patient-derived cells (PDCs) from colony images. Unlike conventional cell lines, PDCs from the tumor are composed of heterogeneous cell populations, and some clonogenic populations form colonies during culture while the rest die off or remain unchanged, thus causing the diverse distribution of colony size. Therefore, area-based analysis of the total colonies is not sufficient to estimate total cell viability or toxicity responses...
February 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28346095/identification-by-high-throughput-screening-of-pseudomonas-acyl-coenzyme-a-synthetase-inhibitors
#2
Lorenzo Turcano, Daniela Visaggio, Emanuela Frangipani, Antonino Missineo, Matteo Andreini, Sergio Altamura, Paolo Visca, Alberto Bresciani
Pseudomonas infections are common among hospitalized, immunocompromised, and chronic lung disease patients. These infections are recalcitrant to common antibacterial therapies due to inherent antibiotic resistance. To meet the need of new anti- Pseudomonas drugs, a sensitive, homogenous, and robust assay was developed with the aim of identifying inhibitors of acyl-coenzyme A synthetases (ACSs) from Pseudomonas. Given the importance of fatty acids for in vivo nutrition of Pseudomonas, such inhibitors might have the potential to reduce the bacterial fitness during infection...
January 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28343740/pediatric-oncology-enters-an-era-of-precision-medicine
#3
Nita L Seibel, Katherine Janeway, Carl E Allen, Susan N Chi, Yoon-Jae Cho, Julia L Glade Bender, AeRang Kim, Theodore W Laetsch, Meredith S Irwin, Naoko Takebe, James V Tricoli, Donald Williams Parsons
With the use of high-throughput molecular profiling technologies, precision medicine trials are ongoing for adults with cancer. Similarly, there is an interest in how these techniques can be applied to tumors in children and adolescents to expand our understanding of the biology of pediatric cancers and evaluate the clinical implications of genomic testing for these patients. This article reviews the early studies in pediatric oncology showing the feasibility of this approach, describe the future plans to evaluate the clinical implications in a multicenter clinical trial and identify the challenges of applying genomics in this patient population...
February 1, 2017: Current Problems in Cancer
https://www.readbyqxmd.com/read/28342926/causes-and-clinical-features-of-infertile-men-with-non-obstructive-azoospermia-and-histopathological-diagnosis-of-hypospermatogenesis
#4
Yu-Sheng Cheng, Chun-Wun Lu, Tsung-Yen Lin, Pei-Yu Lin, Yung-Ming Lin
OBJECTIVE: To analyze the causes and the clinical features of infertile men with non-obstructive azoospermia (NOA) and hypospermatogenesis (HS). METHODS: This retrospective cohort study included 100 patients with NOA and HS and eight patients with obstructive azoospermia and normal spermatogenesis. The severity of HS was subdivided into three groups (mild, moderate, and severe) based on spermatogenic score. Data of history, physical findings, serum hormone profiles, genetic studies and sperm retrieval rate (SRR) were collected...
March 22, 2017: Urology
https://www.readbyqxmd.com/read/28342734/integration-of-microbiome-and-epigenome-to-decipher-the-pathogenesis-of-autoimmune-diseases
#5
REVIEW
Beidi Chen, Luxi Sun, Xuan Zhang
The interaction between genetic predisposition and environmental factors are of great significance in the pathogenesis and development of autoimmune diseases (AIDs). The human mucosa is the most frequent site that interacts with the exterior environment, and commensal microbiota at the gut and other human mucosal cavities play a crucial role in the regulation of immune system. Growing evidence has shown that the compositional and functional changes of mucosal microbiota are closely related to AIDs. Gut dysbiosis not only influence the expression level of Toll-like receptors (TLRs) of antigen presenting cells, but also contribute to Th17/Treg imbalance...
March 22, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28338236/hsa-mir-3199-2-and-hsa-mir-1293-as-novel-prognostic-biomarkers-of-papillary-renal-cell-carcinoma-by-cox-ratio-risk-regression-model-screening
#6
Wen Luo, Lei Wang, Mao-Hua Luo, Yu-Zhu Huang, Hua Yang, Yu Zhou, Hong-Tao Jia, Xiu-Xin Wang
Papillary renal cell carcinoma(PRCC) is the second most common and aggressive renal cell carcinoma. Identification of novel microRNA biomarkers could be beneficial for the diagnosis and prognosis of PRCCpatients.We aimed to screen differentially expressed miRNAs that can act as prognostic factors and to predict the survival of PRCC patients. High-throughput data of miRNAs of 274 PRCC samples were downloaded from TCGA(The Cancer Genome Atlas) dataset and interested miRNAs were identified. Hierarchical clustering and principal component analysis (PCA) were performed on these miRNAs...
March 24, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28337517/a-column-switching-ultrahigh-performance-liquid-chromatography-tandem-mass-spectrometry-method-to-determine-anandamide-and-2-arachidonoylglycerol-in-plasma-samples
#7
Camila Marchioni, Israel Donizeti de Souza, Caroline Fernandes Grecco, José Alexandre Crippa, Vitor Tumas, Maria Eugênia Costa Queiroz
This study reports a fast, sensitive, and selective column switching ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method to determine the endocannabinoids (eCBs), anandamide (AEA), and 2-arachidonoylglycerol (2-AG) in plasma samples. This bidimensional system used a restricted access media column (RP-8 ADS, 25 mm × 4 mm × 25 μM) in the first dimension and a core-shell Kinetex C18 (100 mm × 2, 1.7 mm × 1 μM) column in the second dimension, followed by detection in a mass spectrometer triple quadrupole (multiple reactions monitoring mode) operating in the positive mode...
March 23, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28336564/identification-of-a-novel-syk-c-myc-malat1-signaling-pathway-and-its-potential-therapeutic-value-in-ewing-sarcoma
#8
Haibo Sun, De-Chen Lin, Qi Cao, Brendan Pang, David D Gae, Victor Km Lee, Huey Jin Lim, Ngan Doan, Jonathan W Said, Sigal Gery, Marilynn Chow, Anand Mayakonda, Charles Forscher, Jeffrey W Tyner, H Phillip Koeffler
PURPOSE: Ewing Sarcoma (EWS) is a devastating soft tissue sarcoma affecting predominantly young individuals. Tyrosine kinases (TKs) and associated pathways are continuously activated in many malignancies including EWS; these enzymes provide candidate therapeutic targets. EXPERIMENTAL DESIGN: Two high-throughput screens (a siRNA library and a small-molecule inhibitor library) were performed in EWS cells to establish candidate targets. Spleen tyrosine kinase (SYK) phosphorylation was assessed in EWS patients and cell lines...
March 23, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28334556/impact-of-a-hospitalwide-quality-improvement-initiative-on-emergency-department-throughput-and-crowding-measures
#9
James D Melton, Fred Blind, A Brad Hall, Maureen Leckie, April Novotny
BACKGROUND: This pre- and postintervention analysis evaluates the impact of a systemwide, comprehensive, executively supported quality improvement (QI) project on emergency department (ED) throughput measures and crowding in a large nonacademic community hospital. METHODS: The two primary endpoints used to assess the impact of the project were (1) the percentage of all patients who were door-in to door-out in less than three hours and (2) the percentage of patients who left without being seen (LWBS)...
December 2016: Joint Commission Journal on Quality and Patient Safety
https://www.readbyqxmd.com/read/28334553/a-multi-matrix-hilic-ms-ms-method-for-the-quantitation-of-endogenous-small-molecule-neurological-biomarker-n-acetyl-aspartic-acid-naa
#10
Dewakar Sangaraju, Sheerin K Shahidi-Latham, Braydon L Burgess, Brian Dean, Xiao Ding
A multi-matrix hydrophilic interaction liquid chromatography tandem mass spectrometric method (HILIC-MS/MS) was developed for the quantitation of N-Acetyl Aspartic acid (NAA) using stable isotope labeled internal standard, D3-NAA in various biological matrices such as human plasma, human CSF, mouse plasma, brain and spinal cord. A high throughput 96-well plate format supported liquid extraction (SLE) procedure was developed and used for sample preparation. Mass spectrometric analysis of NAA was performed using selected reaction monitoring transitions in positive electrospray ionization mode...
March 14, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28333338/drug-discovery-for-male-subfertility-using-high-throughput-screening-a-new-approach-to-an-unsolved-problem
#11
Sarah J Martins da Silva, Sean G Brown, Keith Sutton, Louise V King, Halil Ruso, David W Gray, Paul G Wyatt, Mark C Kelly, Christopher L R Barratt, Anthony G Hope
STUDY QUESTION: Can pharma drug discovery approaches be utilized to transform investigation into novel therapeutics for male infertility? SUMMARY ANSWER: High-throughput screening (HTS) is a viable approach to much-needed drug discovery for male factor infertility. WHAT IS KNOWN ALREADY: There is both huge demand and a genuine clinical need for new treatment options for infertile men. However, the time, effort and resources required for drug discovery are currently exorbitant, due to the unique challenges of the cellular, physical and functional properties of human spermatozoa and a lack of appropriate assay platform...
March 16, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28333167/a-complex-intragenic-rearrangement-of-ercc8-in-chinese-siblings-with-cockayne-syndrome
#12
Hua Xie, Xiaoyan Li, Jiping Peng, Qian Chen, ZhiJie Gao, Xiaozhen Song, WeiYu Li, Jianqiu Xiao, Caihua Li, Ting Zhang, James F Gusella, Jianmin Zhong, Xiaoli Chen
Cockayne syndrome is an autosomal recessive disorder principally characterized by postnatal growth failure and progressive neurological dysfunction, due primarily to mutations in ERCC6 and ERCC8. Here, we report our diagnostic experience for two patients in a Chinese family suspected on clinical grounds to have Cockayne syndrome. Using multiple molecular techniques, including whole exome sequencing, array comparative genomic hybridization and quantitative polymerase chain reaction, we identified compound heterozygosity for a maternal splicing variant (chr5:60195556, NM_000082:c...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28333153/a-novel-inhibitor-idpp-interferes-with-entry-and-egress-of-hcv-by-targeting-glycoprotein-e1-in-a-genotype-specific-manner
#13
Myungeun Lee, Jaewon Yang, Eunji Jo, Ji-Young Lee, Hee-Young Kim, Ralf Bartenschlager, Eui-Cheol Shin, Yong-Soo Bae, Marc P Windisch
Despite recent advances in curing chronic hepatitis C (CHC), the high economic burden to therapy, viral drug resistance, difficult to treat hepatitis C virus (HCV) genotypes and patient groups are still of concern. To address this unmet medical needs, we devised strategies to identify novel viral interventions through target-free high-throughput screening of small molecules utilizing a phenotypic-based HCV infection assay. Thereby, a very potent (EC50 46 ± 26 pM) iminodipyridinopyrimidine (IDPP) drug candidate was selected, and confirmed in primary human hepatocytes (EC50 0...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28333087/magnetically-bioprinted-human-myometrial-3d-cell-rings-as-a-model-for-uterine-contractility
#14
Glauco R Souza, Hubert Tseng, Jacob A Gage, Arunmani Mani, Pujan Desai, Fransisca Leonard, Angela Liao, Monica Longo, Jerrie S Refuerzo, Biana Godin
Deregulation in uterine contractility can cause common pathological disorders of the female reproductive system, including preterm labor, infertility, inappropriate implantation, and irregular menstrual cycle. A better understanding of human myometrium contractility is essential to designing and testing interventions for these important clinical problems. Robust studies on the physiology of human uterine contractions require in vitro models, utilizing a human source. Importantly, uterine contractility is a three-dimensionally (3D)-coordinated phenomenon and should be studied in a 3D environment...
March 23, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28331002/personalized-in-vitro-and-in-vivo-cancer-models-to-guide-precision-medicine
#15
Chantal Pauli, Benjamin D Hopkins, Davide Prandi, Reid Shaw, Tarcisio Fedrizzi, Andrea Sboner, Verena Sailer, Michael Augello, Loredana Puca, Rachele Rosati, Terra J McNary, Yelena Churakova, Cynthia Cheung, Joanna Triscott, David Pisapia, Rema Rao, Juan Miguel Mosquera, Brian Robinson, Bishoy M Faltas, Brooke E Emerling, Vijayakrishna K Gadi, Brady Bernard, Olivier Elemento, Himisha Beltran, Francesca Demichelis, Christopher J Kemp, Carla Grandori, Lewis C Cantley, Mark A Rubin
Precision medicine is an approach that takes into account the influence of individuals' genes, environment, and lifestyle exposures to tailor interventions. Here, we describe the development of a robust precision cancer care platform that integrates whole-exome sequencing with a living biobank that enables high-throughput drug screens on patient-derived tumor organoids. To date, 56 tumor-derived organoid cultures and 19 patient-derived xenograft (PDX) models have been established from the 769 patients enrolled in an Institutional Review Board-approved clinical trial...
March 22, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28330689/evaluation-of-methohexital-as-an-alternative-to-propofol-in-a-high-volume-outpatient-pediatric-sedation-service
#16
Nicholas E Jones, Michael S Kelleman, Harold K Simon, Jana A Stockwell, Courtney McCracken, Michael D Mallory, Pradip P Kamat
BACKGROUND: Propofol is a preferred agent for many pediatric sedation providers because of its rapid onset and short duration of action. It allows for quick turn around times and enhanced throughput. Occasionally, intravenous (IV) methohexital (MHX), an ultra-short acting barbiturate is utilized instead of propofol. OBJECTIVE: Describe the experience with MHX in a primarily propofol driven outpatient sedation program and to see if it serves as an acceptable alternative when propofol is not the preferred pharmacologic option...
March 8, 2017: American Journal of Emergency Medicine
https://www.readbyqxmd.com/read/28326956/clinical-pathologic-and-genetic-features-of-wilms-tumors-with-wtx-gene-mutation
#17
Sanda Alexandrescu, Sara Akhavanfard, Marian H Harris, Sara O Vargas
Clinical and pathologic features of patients with WTX-mutated Wilms tumor (WT) have not been studied in detail. We characterize the clinical and pathologic findings in WT with WTX abnormalities and provide comparison with WT without WTX mutation. Clinical, gross, and microscopic features in 35 patients with WT were examined. Karyotype was examined in a subset of cases. All cases had been previously analyzed for WTX, WT1, and CTNNB1 aberrations via array comparative genomic hybridization; OncoMap 4 high throughput genotyping was performed on 18 cases...
March 2017: Pediatric and Developmental Pathology
https://www.readbyqxmd.com/read/28325368/chagas-disease-diagnostic-applications-present-knowledge-and-future-steps
#18
V Balouz, F Agüero, C A Buscaglia
Chagas disease, caused by the protozoan Trypanosoma cruzi, is a lifelong and debilitating illness of major significance throughout Latin America and an emergent threat to global public health. Being a neglected disease, the vast majority of Chagasic patients have limited access to proper diagnosis and treatment, and there is only a marginal investment into R&D for drug and vaccine development. In this context, identification of novel biomarkers able to transcend the current limits of diagnostic methods surfaces as a main priority in Chagas disease applied research...
2017: Advances in Parasitology
https://www.readbyqxmd.com/read/28325207/using-a-systematic-framework-of-interventions-to-improve-early-discharges
#19
Hemali Patel, Sasha Morduchowicz, Michelle Mourad
BACKGROUND: Late-afternoon hospital discharges can lead to admission bottlenecks and negatively affect the flow of patients needing hospital admission. Delays in discharge are a prevalent health care problem and have been linked to increased length of stay, lower patient satisfaction scores, and adverse outcomes. As a result, hospitals are placing a renewed emphasis on early discharge as a way to reduce admission delays and achieve optimal patient flow. This study shows that the Model for Improvement (MFI) is an effective approach for complex improvement efforts...
April 2017: Joint Commission Journal on Quality and Patient Safety
https://www.readbyqxmd.com/read/28323930/%C3%AE-cells-persist-in-t1d-pancreata-without-evidence-for-ongoing-%C3%AE-cell-turnover-or-neogenesis
#20
Carol J Lam, Daniel R Jacobson, Matthew M Rankin, Aaron R Cox, Jake A Kushner
Context: The cellular basis of persistent β-cell function in T1D remains enigmatic. No extensive quantitative β-cell studies of T1D pancreata have been performed to test for ongoing β-cell regeneration or neogenesis. Objective: We sought to determine the mechanism of β-cell persistence in T1D pancreata. Design: We studied T1D (n=47) and non-diabetic control (n=59) pancreata over a wide range of ages from the JDRF Network of Pancreatic Organ donors with Diabetes (nPOD) via high throughput microscopy...
February 27, 2017: Journal of Clinical Endocrinology and Metabolism
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