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https://www.readbyqxmd.com/read/28549280/protocols-for-the-analytical-characterization-of-therapeutic-monoclonal-antibodies-i-non-denaturing-chromatographic-techniques
#1
Alexandre Goyon, Valentina D'Atri, Balazs Bobaly, Elsa Wagner-Rousset, Alain Beck, Szabolcs Fekete, Davy Guillarme
Size-, charge- and hydrophobicity-related variants of a biopharmaceutical product have to be deeply characterized for batch consistency and for the assessment of immunogenicity and safety effects. Size exclusion chromatography (SEC) and ion exchange chromatography (IEX) are considered as the gold standard for the analysis of high molecular weight species (HMWS) and charge-related variants, respectively. Hydrophobic interaction chromatography (HIC) has drawn renewed attention to monitor the small drug payload distribution in the cysteine-linked antibody-drug conjugates (ADC)...
May 11, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28514911/action-learning-across-the-decades
#2
Ken Eason
Purpose The purpose of this paper is to explore how action learning concepts were used in two healthcare projects undertaken many decades apart. The specific purpose in both cases was to examine how action learning can contribute to shared learning across key stakeholders in a complex socio-technical system. In each case study, action learning supported joint design programmes and the sharing of perspectives about the complex system under investigation. Design/methodology/approach Two action learning projects are described: first, the Hospital Internal Communications (HIC) project led by Reg Revans in the 1960s...
May 2, 2017: Leadership in Health Services
https://www.readbyqxmd.com/read/28513628/an-integrated-model-for-detecting-significant-chromatin-interactions-from-high-resolution-hi-c-data
#3
Mark Carty, Lee Zamparo, Merve Sahin, Alvaro González, Raphael Pelossof, Olivier Elemento, Christina S Leslie
Here we present HiC-DC, a principled method to estimate the statistical significance (P values) of chromatin interactions from Hi-C experiments. HiC-DC uses hurdle negative binomial regression account for systematic sources of variation in Hi-C read counts-for example, distance-dependent random polymer ligation and GC content and mappability bias-and model zero inflation and overdispersion. Applied to high-resolution Hi-C data in a lymphoblastoid cell line, HiC-DC detects significant interactions at the sub-topologically associating domain level, identifying potential structural and regulatory interactions supported by CTCF binding sites, DNase accessibility, and/or active histone marks...
May 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28504544/radial-ultrashort-te-imaging-removes-the-need-for-breath-holding-in-hepatic-iron-overload-quantification-by-r2-mri
#4
Aaryani Tipirneni-Sajja, Axel J Krafft, M Beth McCarville, Ralf B Loeffler, Ruitian Song, Jane S Hankins, Claudia M Hillenbrand
OBJECTIVE: The objective of this study is to evaluate radial free-breathing (FB) multiecho ultrashort TE (UTE) imaging as an alternative to Cartesian FB multiecho gradient-recalled echo (GRE) imaging for quantitative assessment of hepatic iron content (HIC) in sedated patients and subjects unable to perform breath-hold (BH) maneuvers. MATERIALS AND METHODS: FB multiecho GRE imaging and FB multiecho UTE imaging were conducted for 46 test group patients with iron overload who could not complete BH maneuvers (38 patients were sedated, and eight were not sedated) and 16 control patients who could complete BH maneuvers...
May 15, 2017: AJR. American Journal of Roentgenology
https://www.readbyqxmd.com/read/28488758/engineered-humicola-insolens-cutinase-for-efficient-cellulose-acetate-deacetylation
#5
Abhijit N Shirke, Glenn L Butterfoss, Rakhi Saikia, Aditya Basu, Leonardo de Maria, Allan Svendsen, Richard A Gross
Cutinases comprise a family of esterases with broad hydrolytic activity for chain and pendant ester groups. This work aimed to identify and improve an efficient cutinase for cellulose acetate (CA) deacetylation. The development of a mild method for CA fiber surface deacetylation will result in improved surface hydrophilicity and reactivity while, when combined with cellulases, a route to the full recycling of CA to acetate and glucose. In this study, the comparative CA deacetylation activity of 4 homologous wild-type (wt) fungal cutinases from Aspergillus oryzae (AoC), Thiellavia terrestris (TtC), Fusarium solani (FsC), and Humicola insolens (HiC) was determined by analysis of CA deacetylation kinetics...
May 10, 2017: Biotechnology Journal
https://www.readbyqxmd.com/read/28487456/deriving-literature-based-benchmarks-for-surgical-complications-in-high-income-countries-a-protocol-for-a-systematic-review-and-meta-analysis
#6
Mary E Brindle, Derek J Roberts, Oluwatomilayo Daodu, Alex Bernard Haynes, Christy Cauley, Elijah Dixon, Claude La Flamme, Paul Bain, William Berry
INTRODUCTION: To improve surgical safety, health systems must identify preventable adverse outcomes and measure changes in these outcomes in response to quality improvement initiatives. This requires understanding of the scope and limitations of available population-level data. To derive literature-based summary estimates of benchmarks of care, we will systematically review and meta-analyse rates of postoperative complications associated with several common and/or high-risk operations performed in five high-income countries (HICs)...
May 9, 2017: BMJ Open
https://www.readbyqxmd.com/read/28485144/hydrophobic-interaction-chromatography-for-bottom-up-proteomics-analysis-of-single-proteins-and-protein-complexes
#7
Michal Rackiewicz, Ludger Große-Hovest, Andrew J Alpert, Mostafa Zarei, Jörn Dengjel
Hydrophobic interaction chromatography (HIC) is a robust standard analytical method to purify proteins while preserving their biological activity. It is widely used to study post-translational modifications of proteins and drug-protein interactions. In the current manuscript we employed HIC to separate proteins, followed by bottom-up LC-MS/MS experiments. We used this approach to fractionate antibody species followed by comprehensive peptide mapping as well as to study protein complexes in human cells. HIC-reversed-phase chromatography (RPC)-mass spectrometry (MS) is a powerful alternative to fractionate proteins for bottom-up proteomics experiments making use of their distinct hydrophobic properties...
May 11, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28465695/benefits-barriers-and-limitations-on-the-use-of-hospital-incident-command-system
#8
REVIEW
Shahin Shooshtari, Shahram Tofighi, Shirin Abbasi
Hospital Incident Command System (HICS) has been established with the mission of prevention, response, and recovery in hazards. Regarding the key role of hospitals in medical management of events, the present study is aimed at investigating benefits, barriers, and limitations of applying HICS in hospital. Employing a review study, articles related to the aforementioned subject published from 1995 to 2016 were extracted from accredited websites and databases such as PubMed, Google Scholar, Elsevier, and SID by searching keywords such as HICS, benefits, barriers, and limitations...
2017: Journal of Research in Medical Sciences: the Official Journal of Isfahan University of Medical Sciences
https://www.readbyqxmd.com/read/28463561/discovery-of-novel-and-selective-adenosine-a2a-receptor-antagonists-for-treating-parkinson-s-disease-through-comparative-structure-based-virtual-screening
#9
Sheng Tian, Xu Wang, Linlang Li, Xiaohu Zhang, Youyong Li, Feng Zhu, Tingjun Hou, Xuechu Zhen
Among non-dopaminergic strategies for combating Parkinson's disease (PD), antagonism of the A2A adenosine receptor (AR) has emerged to show great potential. In this study, on the basis of two crystal structures of the A2A AR with the best capability to distinguish known antagonists from decoys, docking-based virtual screening (VS) was conducted to identify novel A2A AR antagonists. A total of 63 structurally diverse compounds identified by VS were submitted to experimental testing, and 11 of them exhibited substantial activity against the A2A AR (Ki < 10 μM), including two compounds with Ki below 1 μM (compound 43, 0...
May 15, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28458283/the-characterization-of-drug-to-antibody-ratio-and-isoforms-of-adcs-using-lc-and-ms-technologies
#10
Reiko Iizuka, Frank Kotch, April Xu, Thomas Porter, Henry Shion, Robert Birdsall, Weibin Chen
 Hydrophobic interaction chromatography (HIC) and MS are leading techniques for the characterization of the critical quality attributes (CQA) of antibody-drug conjugates (ADCs). This includes the average drug-to-antibody ratio (DAR) and drug loading distribution. A workflow that effectively utilizes the synergy between chromatography and detection technologies has been developed and was assessed using cysteine-conjugated ADCs. The DAR of low, moderate and high drug-loaded ADC samples were calculated from the chromatographic peak areas using LC(HIC)/UV or the deconvoluted mass spectra using native LC(SEC)/MS...
2017: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/28452653/the-medical-education-partnership-initiative-mepi-a-collaborative-paradigm-for-institutional-and-human-resources-capacity-building-between-high-and-low-and-middle-income-countries-the-mozambique-experience
#11
Emília Virgínia Noormahomed, Carla Carrilho, Mamudo Ismail, Sérgio Noormahomed, Alcido Nguenha, Constance A Benson, Ana Olga Mocumbi, Robert T Schooley
BACKGROUND: Collaborations among researchers based in lower and middle income countries (LMICs) and high income countries (HICs) have made major discoveries related to diseases disproportionately affecting LMICs and have been vital to the development of research communities in LMICs. Such collaborations have generally been scientifically and structurally driven by HICs. OBJECTIVES: In this report we outline a paradigm shift in collaboration, exemplified by the Medical Education Partnership Initiative (MEPI), in which the formulation of priorities and administrative infrastructure reside in the LMIC...
2017: Global Health Action
https://www.readbyqxmd.com/read/28442372/long-term-release-and-stability-of-pharmaceutical-proteins-delivered-from-solid-lipid-implants
#12
Moritz Vollrath, Julia Engert, Gerhard Winter
Solid lipid implants (SLIs) prepared by twin-screw (tsc) extrusion represent a promising technology platform for the sustained release of pharmaceutical proteins. In this work, we report on two aspects, long-term release and stability of released protein. First, SLIs were produced by tsc-extrusion containing the low melting triglyceride H12 and the high melting triglyceride Dynasan D118. Two different proteins available in a freeze-dried matrix containing hydroxypropyl-β-cyclodextrine (HP-β-CD) were incorporated into the lipid matrix: a monoclonal antibody (mAb) from the IgG1 class and the fab-fragment Ranibizumab (Lucentis(®))...
April 22, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28431498/migrant-workers-in-italy-an-analysis-of-injury-risk-taking-into-account-occupational-characteristics-and-job-tenure
#13
Massimiliano Giraudo, Antonella Bena, Giuseppe Costa
BACKGROUND: Migrants resident in Italy exceeded 5 million in 2015, representing 8.2% of the resident population. The study of the mechanisms that explain the differential health of migrant workers (as a whole and for specific nationalities) has been identified as a priority for research. The international literature has shown that migrant workers have a higher risk of total and fatal injury than natives, but some results are conflicting. The aim of this paper is to study the injury risk differentials between migrants, born in countries with strong migratory pressure (SMPC), and workers born in high income countries (HIC), taking into account individual and firm characteristics and job tenure...
April 22, 2017: BMC Public Health
https://www.readbyqxmd.com/read/28427373/a-protocol-for-a-cluster-randomized-controlled-trial-of-a-self-help-psycho-education-programme-to-reduce-diagnosis-delay-in-women-with-breast-cancer-symptoms-in-indonesia
#14
Hari Setyowibowo, Marit Sijbrandij, Aulia Iskandarsyah, Joke A M Hunfeld, Sawitri S Sadarjoen, Dharmayanti F Badudu, Drajat R Suardi, Jan Passchier
BACKGROUND: Breast cancer (BC) is the most frequent cancer occurring in women across the world. Its mortality rate in low-middle income countries (LMICs) is higher than in high-income countries (HICs), and in Indonesia BC is the leading cause of cancer deaths among women. Delay in breast cancer diagnosis negatively impacts cancer prognosis. Only about 30% of patients who come to the hospital to check on their breast abnormalities, continue thorough examination to biopsy to get a diagnosis based on the results of anatomical pathology...
April 20, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28420405/do-international-health-partnerships-contribute-to-reverse-innovation-a-mixed-methods-study-of-thet-supported-partnerships-in-the-uk
#15
Kavian Kulasabanathan, Hamdi Issa, Yasser Bhatti, Matthew Prime, Jacqueline Del Castillo, Ara Darzi, Matthew Harris
BACKGROUND: International health partnerships (IHPs) are changing, with an increased emphasis on mutual accountability and joint agenda setting for both the high- and the low- or middle-income country (LMIC) partners. There is now an important focus on the bi-directionality of learning however for the UK partners, this typically focuses on learning at the individual level, through personal and professional development. We sought to evaluate whether this learning also takes the shape of 'Reverse Innovation' -when an idea conceived in a low-income country is subsequently adopted in a higher-income country...
April 18, 2017: Globalization and Health
https://www.readbyqxmd.com/read/28409537/impact-of-pneumococcal-conjugate-vaccines-for-children-in-high-and-non-high-income-countries
#16
Robert Cohen, Jérémie François Cohen, Martin Chalumeau, Corinne Levy
The high level of effectiveness of pneumococcal conjugate vaccines (PCVs) was demonstrated initially in high-income countries (HICs). However, because the burden of pneumococcal diseases (PDs) is greater in non-high-income countries (NHICs) than HICs, the assessment of these vaccines in this latter setting is crucial. Areas covered: PubMed was used to search for literature related to the effectiveness of PCVs. Several studies described the effectiveness of PCVs in NHICs, and we compare the impact of PCVs on the incidence of invasive pneumococcal disease (IPD) and pneumonia in HICs and NHICs...
April 28, 2017: Expert Review of Vaccines
https://www.readbyqxmd.com/read/28389488/secular-trends-in-the-incidence-of-dementia-in-high-income-countries-a-protocol-of-a-systematic-review-and-a-planned-meta-analysis
#17
Susanne Roehr, Alexander Pabst, Tobias Luck, Steffi G Riedel-Heller
INTRODUCTION: A global dementia epidemic is projected for the year 2050 with an ever-rising number of individuals living with the syndrome worldwide. However, increasingly, studies are emerging from high-income countries (HIC) that show a positive trend towards a possible decrease in dementia occurrence. Therefore, we aim to systematically summarise evidence regarding secular trends in the incidence of dementia in HIC. METHODS AND ANALYSIS: We will conduct a systematic review of the literature on secular trends in dementia incidence in HIC according to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and the Meta-analysis of Observational Studies in Epidemiology (MOOSE) statements...
April 7, 2017: BMJ Open
https://www.readbyqxmd.com/read/28388437/the-bet-protein-brd2-cooperates-with-ctcf-to-enforce-transcriptional-and-architectural-boundaries
#18
Sarah C Hsu, Thomas G Gilgenast, Caroline R Bartman, Christopher R Edwards, Aaron J Stonestrom, Peng Huang, Daniel J Emerson, Perry Evans, Michael T Werner, Cheryl A Keller, Belinda Giardine, Ross C Hardison, Arjun Raj, Jennifer E Phillips-Cremins, Gerd A Blobel
Bromodomain and extraterminal motif (BET) proteins are pharmacologic targets for the treatment of diverse diseases, yet the roles of individual BET family members remain unclear. We find that BRD2, but not BRD4, co-localizes with the architectural/insulator protein CCCTC-binding factor (CTCF) genome-wide. CTCF recruits BRD2 to co-bound sites whereas BRD2 is dispensable for CTCF occupancy. Disruption of a CTCF/BRD2-occupied element positioned between two unrelated genes enables regulatory influence to spread from one gene to another, suggesting that CTCF and BRD2 form a transcriptional boundary...
April 6, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28383545/the-collaborative-african-genomics-network-training-program-a-trainee-perspective-on-training-the-next-generation-of-african-scientists
#19
Busisiwe C Mlotshwa, Savannah Mwesigwa, Gerald Mboowa, Lesedi Williams, Gaone Retshabile, Adeodata Kekitiinwa, Misaki Wayengera, Samuel Kyobe, Chester W Brown, Neil A Hanchard, Graeme Mardon, Moses Joloba, Gabriel Anabwani, Sununguko W Mpoloka
PURPOSE: The Collaborative African Genomics Network (CAfGEN) aims to establish sustainable genomics research programs in Botswana and Uganda through long-term training of PhD students from these countries at Baylor College of Medicine. Here, we present an overview of the CAfGEN PhD training program alongside trainees' perspectives on their involvement. BACKGROUND: Historically, collaborations between high-income countries (HICs) and low- and middle-income countries (LMICs), or North-South collaborations, have been criticized for the lack of a mutually beneficial distribution of resources and research findings, often undermining LMICs...
April 6, 2017: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/28381557/glucocorticoid-receptor-binding-to-chromatin-is-selectively-controlled-by-coregulator-hic-5-and-chromatin-remodeling-enzymes
#20
Brian H Lee, Michael R Stallcup
The steroid hormone-activated glucocorticoid receptor (GR) regulates cellular stress pathways by binding to genomic regulatory elements of target genes and recruiting coregulator proteins to remodel chromatin and regulate transcription complex assembly. The coregulator Hydrogen peroxide-inducible clone 5 (Hic-5) is required for glucocorticoid (GC) regulation of some genes, but not others, and blocks regulation of a third gene set by inhibiting GR binding. How Hic-5 exerts these gene-specific effects, and specifically how it blocks GR binding to some genes but not others is unclear...
April 5, 2017: Journal of Biological Chemistry
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