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https://www.readbyqxmd.com/read/28737744/delivering-advanced-therapies-the-big-pharma-approach
#1
REVIEW
J Tarnowski, D Krishna, L Jespers, A Ketkar, R Haddock, J Imrie, S Kili
After two decades of focused development and some recent clinical successes, cell and gene therapy (CGT) is emerging as a promising approach to personalized medicines. Genetically engineered cells as a medical modality are poised to stand alongside or in combination with small molecule and biopharmaceutical approaches to bring new therapies to patients globally. Big pharma can play a vital role in industrializing CGT by focusing on diseases with high un-met medical need and compelling genetic evidence. Pharma should invest in manufacturing and supply chain solutions that deliver reproducible, high quality therapies at a commercially viable cost...
July 24, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28736627/personalized-and-precision-medicine-integrating-genomics-into-treatment-decisions-in-gastrointestinal-malignancies
#2
REVIEW
Trang H Au, Kai Wang, David Stenehjem, Ignacio Garrido-Laguna
The advent of next generation sequencing (NGS) technologies has advanced our understanding of the intrinsic biology of different gastrointestinal (GI) tumor types. The use of novel, more efficient sequencing platforms has improved turnaround times of sequencing results. This is providing real time opportunities to put precision medicine to the test. A number of early phase clinical trials are testing targeted therapies in unique molecularly characterized subsets of patients (baskets). While basket studies are gaining momentum, treatment failures serve to remind us that shifting from a histology-driven to a histology-agnostic approach is unlikely to be a failure-free strategy for a number of tumor types as recently learnt from vemurafenib failure in BRAF mutated metastatic colorectal cancer (mCRC)...
June 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28736396/using-theories-of-practice-to-understand-hiv-positive-persons-varied-engagement-with-hiv-services-a-qualitative-study-in-six-sub-saharan-african-countries
#3
Morten Skovdal, Alison Wringe, Janet Seeley, Jenny Renju, Sara Paparini, Joyce Wamoyi, Mosa Moshabela, William Ddaaki, Constance Nyamukapa, Kenneth Ondenge, Sarah Bernays, Oliver Bonnington
OBJECTIVES: This article considers the potential of 'theories of practice' for studying and understanding varied (dis)engagement with HIV care and treatment services and begins to unpack the assemblage of elements and practices that shape the nature and duration of individuals' interactions with HIV services. METHODS: We obtained data from a multicountry qualitative study that explores the use of HIV care and treatment services, with a focus on examining the social organisation of engagement with care as a practice and as manifested in the lives of people living with HIV in sub-Saharan Africa...
July 2017: Sexually Transmitted Infections
https://www.readbyqxmd.com/read/28736271/b-cells-and-their-cytokine-activities-implications-in-human-diseases
#4
Simon Fillatreau
B cells are the only cell type that can give rise to antibody-producing cells, and the only cell type whose selective depletion can, today, lead to an improvement of a wide range of immune-mediated inflammatory diseases, including disorders not primarily driven by autoantibodies. Here, I discuss this paradoxical observation, and propose that the capacity of B cells to act as cytokine-producing cells explains how they can control monocyte activity and subsequently disease pathogenesis. Together with current data on the effect of anti-CD20 B cell-depleting reagents in the clinic, this novel knowledge on B cell heterogeneity opens the way for novel safer and more efficient strategies to target B cells...
July 20, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28736238/the-pursuit-of-therapeutic-biomarkers-with-high-throughput-cancer-cell-drug-screens
#5
REVIEW
Steven P Williams, Ultan McDermott
In the last decade we have witnessed tremendous advances in our understanding of the landscape of the molecular alterations that underpin many of the most prevalent cancers, in the use of automated high-throughput platforms for high-throughput drug screens in cancer cells, in the creation of more clinically relevant cancer cell models, and lastly in the development of more useful computational approaches in the pursuit of biomarkers of drug response. Separately, each of these improvements will undoubtedly lead to improvements in the treatment of cancer patients but to fulfill the promise of truly personalized cancer medicine, we must bring these disciplines together in a truly multidisciplinary fashion...
July 12, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28735342/cataract-in-the-chronically-exposed-residents-of-the-techa-riverside-villages
#6
L D Mikryukova, A V Akleyev
The present study is based on a retrospective analysis of archive data of the Clinical Department of the Urals Research Center for Radiation Medicine that has been established to examine and treat accidentally exposed residents of the Urals Region. All individuals included in this study were examined by an ophthalmologist. The study of cataract incidence has been conducted retrospectively for the period from 1951 till 2000 among chronically exposed residents of the Techa riverside villages (6343 persons). Individual accumulated absorbed doses to soft tissues (analogue of eye dose) reached 1...
July 22, 2017: Radiation and Environmental Biophysics
https://www.readbyqxmd.com/read/28734859/provider-health-and-wellness
#7
REVIEW
Anil Nanda, Anita Wasan, James Sussman
Provider health and wellness is a significant issue and can impact patient care, including patient satisfaction, quality of care, medical errors, malpractice risk, as well as provider and office staff turnover and early retirement. Health and wellness encompasses various areas including burnout, depression, divorce, and suicide and affects providers of all specialties and at all levels of training. Providers deal with many everyday stresses, including electronic health records, office politics, insurance and billing issues, dissatisfied patients, and their own personal and family issues...
July 19, 2017: Journal of Allergy and Clinical Immunology in Practice
https://www.readbyqxmd.com/read/28733920/complementary-and-alternative-medicine-among-persons-living-with-hiv-in-the-era-of-combined-antiretroviral-treatment
#8
Sean N Halpin, Edwin Clayton Carruth, Ramona P Rai, E Jennifer Edelman, David A Fiellin, Cynthia Gibert, Kirsha S Gordon, Wei Huang, Amy Justice, Vincent C Marconi, David Rimland, Molly M Perkins
Complementary and alternative medicine (CAM), often pursued independent of prescribing clinicians, may interact with traditional treatments, yet CAM use has not been well characterized among people living with HIV (PLWH) in the combined antiretroviral therapy (ART) era. We analyzed data from the Veterans Aging Cohort Study (October 2012-April 2015) to characterize CAM use in PLWH on ART. CAM users were more likely to have lived longer with HIV, report more bothersome symptoms, be prescribed more benzodiazepines and opioids, and consume less nicotine and alcohol...
July 21, 2017: AIDS and Behavior
https://www.readbyqxmd.com/read/28733374/the-fallacy-of-average-how-using-hba1c-alone-to-assess-glycemic-control-can-be-misleading
#9
Roy W Beck, Crystal G Connor, Deborah M Mullen, David M Wesley, Richard M Bergenstal
HbA1c is a valuable metric for comparing treatment groups in a randomized trial, for assessing glycemic trends in a population over time, or for cross-sectional comparisons of glycemic control in different populations. However, what is not widely appreciated is that HbA1c may not be a good indicator of an individual patient's glycemic control because of the wide range of mean glucose concentrations and glucose profiles that can be associated with a given HbA1c level. To illustrate this point, we plotted mean glucose measured with continuous glucose monitoring (CGM) versus central laboratory-measured HbA1c in 387 participants in three randomized trials, showing that not infrequently HbA1c may underestimate or overestimate mean glucose, sometimes substantially...
August 2017: Diabetes Care
https://www.readbyqxmd.com/read/28733182/the-association-of-depressive-symptoms-with-rates-of-acute-exacerbations-in-patients-with-copd-results-from-a-3-year-longitudinal-follow-up-of-the-eclipse-cohort
#10
Abebaw Mengistu Yohannes, Hana Mülerová, Kim Lavoie, Jorgen Vestbo, Steve I Rennard, Emile Wouters, Nicola A Hanania
BACKGROUND: Depression increases disability and health care utilization in older patients with chronic obstructive pulmonary disease (COPD). OBJECTIVES: To determine contribution of depressive symptoms to the incidence of moderate-severe and severe acute exacerbations of COPD (AECOPD) over 3 years. DESIGN: We analyzed data collected from a prospective cohort of patients with COPD (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints; ECLIPSE)...
July 18, 2017: Journal of the American Medical Directors Association
https://www.readbyqxmd.com/read/28732379/integrative-analysis-of-novel-hypomethylation-and-gene-expression-signatures-in-glioblastomas
#11
Anan Yin, Amandine Etcheverry, Yalong He, Marc Aubry, Jill Barnholtz-Sloan, Luhua Zhang, Xinggang Mao, Weijun Chen, Bolin Liu, Wei Zhang, Jean Mosser, Xiang Zhang
Molecular and clinical heterogeneity critically hinders better treatment outcome for glioblastomas (GBMs); integrative analysis of genomic and epigenomic data may provide useful information for improving personalized medicine. By applying training-validation approach, we identified a novel hypomethylation signature comprising of three CpGs at non-CpG island (CGI) open sea regions for GBMs. The hypomethylation signature consistently predicted poor prognosis of GBMs in a series of discovery and validation datasets...
July 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28731962/polymorphisms-in-cytochrome-p450-oxidoreductase-and-its-effect-on-drug-metabolism-and-efficacy
#12
Liang Gong, Cong-Min Zhang, Jin-Feng Lv, Hong-Hao Zhou, Lan Fan
Cytochrome P450 oxidoreductase (POR) has played a potential role in the metabolism of drugs and steroids by supplying electrons to microsomal cytochrome P450 (CYP) enzymes. More than 200 different POR mutations and polymorphisms causing more than 130 amino acid changes in the POR protein have been reported since 2004. A503V is a common amino acid sequence variant encoded by POR*28, whereas A287P and R457H are the most common disease-causing mutations in Europeans and Asians, respectively. Polymorphisms in the POR gene can affect POR activity, CYP-mediated drug metabolism activities, and the efficacy of several clinically used drugs...
July 20, 2017: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/28731273/scaffold-free-liver-on-a-chip-with-multiscale-organotypic-cultures
#13
Yu-Shih Weng, Shau-Feng Chang, Ming-Cheng Shih, Shih-Heng Tseng, Chih-Huang Lai
The considerable advances that have been made in the development of organotypic cultures have failed to overcome the challenges of expressing tissue-specific functions and complexities, especially for organs that require multitasking and complex biological processes, such as the liver. Primary liver cells are ideal biological building blocks for functional organotypic reconstruction, but are limited by their rapid loss of physiological integrity in vitro. Here the concept of lattice growth used in material science is applied to develop a tissue incubator, which provides physiological cues and controls the 3D assembly of primary cells...
July 21, 2017: Advanced Materials
https://www.readbyqxmd.com/read/28730671/many-faces-of-rationality-implications-of-the-great-rationality-debate-for-clinical-decision-making
#14
Benjamin Djulbegovic, Shira Elqayam
Given that more than 30% of healthcare costs are wasted on inappropriate care, suboptimal care is increasingly connected to the quality of medical decisions. It has been argued that personal decisions are the leading cause of death, and 80% of healthcare expenditures result from physicians' decisions. Therefore, improving healthcare necessitates improving medical decisions, ie, making decisions (more) rational. Drawing on writings from The Great Rationality Debate from the fields of philosophy, economics, and psychology, we identify core ingredients of rationality commonly encountered across various theoretical models...
July 20, 2017: Journal of Evaluation in Clinical Practice
https://www.readbyqxmd.com/read/28730264/is-the-human-embryo-legally-defined-and-protected-causes-and-consequences
#15
Maria Aluaş, Claudia Diana Gherman, Cristiana Iulia Dumitrescu
"Everyone's right to life shall be protected by law", states the article 2 of the European Convention of Human Rights (1950). This article guarantees the protection of life of all persons. The human embryo, however, does not seem to be under the protection of this article, or, at least not always. The human embryo does not have a nature clearly defined and it is not considered always as person. The law protects only two categories by its ordinary regulations: things and persons. Our main objective is to find out if the human embryo is or not protected, according to the legal framework in Romania...
2017: Romanian Journal of Morphology and Embryology, Revue Roumaine de Morphologie et Embryologie
https://www.readbyqxmd.com/read/28729958/mutational-analysis-of-driver-genes-with-tumor-suppressive-and-oncogenic-roles-in-gastric-cancer
#16
Tianfang Wang, Yining Liu, Min Zhao
Gastric cancer (GC) is a complex disease with heterogeneous genetic mechanisms. Genomic mutational profiling of gastric cancer not only expands our knowledge about cancer progression at a fundamental genetic level, but also could provide guidance on new treatment decisions, currently based on tumor histology. The fact that precise medicine-based treatment is successful in a subset of tumors indicates the need for better identification of clinically related molecular tumor phenotypes, especially with regard to those driver mutations on tumor suppressor genes (TSGs) and oncogenes (ONGs)...
2017: PeerJ
https://www.readbyqxmd.com/read/28729804/a-case-of-tooth-fracture-occurred-upon-medicating-bisphosphonate-for-an-elderly-person-preservation-therapy-and-responses-for-stage-0-of-bisphosphonate-related-osteonecrosis-of-jaw
#17
Noriko Suzuki, Hitoshi Oguchi, Yu Yamauchi, Yasuyo Karube, Yukimi Suzuki, Noriyasu Hosoya
This case report aimed to report the progress of preservation therapy and response of symptoms and signs for Stage 0 of bisphosphonate-related osteonecrosis of jaw (BRONJ). A 68-year-old female was recognized having a tooth at the left upper first molar fracture upon medicating bisphosphonate (BP) in 2007. At that time, the extraction of the tooth was an absolute contraindication. Therefore, we performed preservation therapy. We observed the symptoms and signs every month. After 5 months, swelling and redness in the entire first molar tooth were seen and fistula formed partly...
April 2017: European Journal of Dentistry
https://www.readbyqxmd.com/read/28726855/cyclodextrin-based-biological-stimuli-responsive-carriers-for-smart-and-precision-medicine
#18
Rongqiang Liao, Pin Lv, Qian Wang, Jiaoni Zheng, Bing Feng, Bo Yang
Spurred on by recent progress in nanotechnology and precision medicine, smart drug carriers are entering an entirely new era. Smart drug carriers have been widely studied in recent years as a result of their ability to control drug release under different microenvironments (such as pH, redox, and enzyme) in vivo. Host-guest interactions based on cyclodextrins have proven to be an efficient tool for fabricating smart drug carriers. Because of the application of host-guest interactions, many kinds of biological molecules or supramolecular building blocks can combine into an organic whole at the molecular level...
July 20, 2017: Biomaterials Science
https://www.readbyqxmd.com/read/28726812/a-patient-with-germ-line-gain-of-function-pdgfrb-p-n666h-mutation-and-marked-clinical-response-to-imatinib
#19
Dinel Pond, Florence A Arts, Nancy J Mendelsohn, Jean-Baptiste Demoulin, Gunter Scharer, Yoav Messinger
PurposeHeterozygous germ-line activating mutations in PDGFRB cause Kosaki and Penttinen syndromes and myofibromatosis. We describe a 10-year-old child with a germ-line PDGFRB p.N666H mutation who responded to the tyrosine kinase inhibitor imatinib by inhibition of PDGFRB.MethodsThe impact of p.N666H on PDGFRB function and sensitivity to imatinib was studied in cell culture.ResultsCells expressing the p.N666H mutation showed constitutive PDGFRB tyrosine phosphorylation. PDGF-independent proliferation was abolished by imatinib at 1 μM concentration...
July 20, 2017: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/28726810/a-randomized-controlled-trial-of-disclosing-genetic-risk-information-for-alzheimer-disease-via-telephone
#20
Kurt D Christensen, Wendy R Uhlmann, J Scott Roberts, Erin Linnenbringer, Peter J Whitehouse, Charmaine D M Royal, Thomas O Obisesan, L Adrienne Cupples, Melissa B Butson, Grace-Ann Fasaye, Susan Hiraki, Clara A Chen, Uwe Siebert, Robert Cook-Deegan, Robert C Green
PurposeTelephone disclosure of genetic test results can improve access to services. To date, studies of its impact have focused on return of Mendelian risk information, principally hereditary cancer syndromes.MethodsIn a multisite trial of Alzheimer disease genetic risk disclosure, asymptomatic adults were randomized to receive test results in person or via telephone. Primary analyses examined patient outcomes 12 months after disclosure.ResultsData from 257 participants showed that telephone disclosure occurred 7...
July 20, 2017: Genetics in Medicine: Official Journal of the American College of Medical Genetics
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