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https://www.readbyqxmd.com/read/28928729/high-throughput-genetic-screen-reveals-that-early-attachment-and-biofilm-formation-are-necessary-for-full-pyoverdine-production-by-pseudomonas-aeruginosa
#1
Donghoon Kang, Natalia V Kirienko
Pseudomonas aeruginosa is a re-emerging, multidrug-resistant, opportunistic pathogen that threatens the lives of immunocompromised patients, patients with cystic fibrosis, and those in critical care units. One of the most important virulence factors in this pathogen is the siderophore pyoverdine. Pyoverdine serves several critical roles during infection. Due to its extremely high affinity for ferric iron, pyoverdine gives the pathogen a significant advantage over the host in their competition for iron. In addition, pyoverdine can regulate the production of multiple bacterial virulence factors and perturb host mitochondrial homeostasis...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28922229/micrornas-as-clinical-biomarkers-and-therapeutic-tools-in-perioperative-medicine
#2
Simone Kreth, Max Hübner, Ludwig Christian Hinske
Over the past decade, evolutionarily conserved, noncoding small RNAs-so-called microRNAs (miRNAs)-have emerged as important regulators of virtually all cellular processes. miRNAs influence gene expression by binding to the 3'-untranslated region of protein-coding RNA, leading to its degradation and translational repression. In medicine, miRNAs have been revealed as novel, highly promising biomarkers and as attractive tools and targets for novel therapeutic approaches. miRNAs are currently entering the field of perioperative medicine, and they may open up new perspectives in anesthesia, critical care, and pain medicine...
September 14, 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28919307/a-journey-between-high-altitude-hypoxia-and-critical-patient-hypoxia-what-can-it-teach-us-about-compression-and-the-management-of-critical-disease
#3
M L Avellanas Chavala
High altitude sickness (hypobaric hypoxia) is a form of cellular hypoxia similar to that suffered by critically ill patients. The study of mountaineers exposed to extreme hypoxia offers the advantage of involving a relatively homogeneous and healthy population compared to those typically found in Intensive Care Units (ICUs), which are heterogeneous and generally less healthy. Knowledge of altitude physiology and pathology allows us to understanding how hypoxia affects critical patients. Comparable changes in mitochondrial biogenesis between both groups may reflect similar adaptive responses and suggest therapeutic interventions based on the protection or stimulation of such mitochondrial biogenesis...
September 14, 2017: Medicina Intensiva
https://www.readbyqxmd.com/read/28915335/ecm-related-myopathies-and-muscular-dystrophies-pros-and-cons-of-protein-therapies
#4
Pam M Van Ry, Tatiana M Fontelonga, Pamela Barraza-Flores, Apurva Sarathy, Andreia M Nunes, Dean J Burkin
Extracellular matrix (ECM) myopathies and muscular dystrophies are a group of genetic diseases caused by mutations in genes encoding proteins that provide critical links between muscle cells and the extracellular matrix. These include structural proteins of the ECM, muscle cell receptors, enzymes, and intracellular proteins. Loss of adhesion within the myomatrix results in progressive muscle weakness. For many ECM muscular dystrophies, symptoms can occur any time after birth and often result in reduced life expectancy...
September 12, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28902596/evaluation-of-a-rapid-molecular-drug-susceptibility-test-for-tuberculosis
#5
Yingda L Xie, Soumitesh Chakravorty, Derek T Armstrong, Sandra L Hall, Laura E Via, Taeksun Song, Xing Yuan, Xiaoying Mo, Hong Zhu, Peng Xu, Qian Gao, Myungsun Lee, Jongseok Lee, Laura E Smith, Ray Y Chen, Joon Sung Joh, YoungSoo Cho, Xin Liu, Xianglin Ruan, Lili Liang, Nila Dharan, Sang-Nae Cho, Clifton E Barry, Jerrold J Ellner, Susan E Dorman, David Alland
BACKGROUND: Fluoroquinolones and second-line injectable drugs are the backbone of treatment regimens for multidrug-resistant tuberculosis, and resistance to these drugs defines extensively drug-resistant tuberculosis. We assessed the accuracy of an automated, cartridge-based molecular assay for the detection, directly from sputum specimens, of Mycobacterium tuberculosis with resistance to fluoroquinolones, aminoglycosides, and isoniazid. METHODS: We conducted a prospective diagnostic accuracy study to compare the investigational assay against phenotypic drug-susceptibility testing and DNA sequencing among adults in China and South Korea who had symptoms of tuberculosis...
September 14, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28876137/penetrance-and-the-healthy-elderly
#6
Paul Lacaze, Ingrid Winship, John McNeil
The variable penetrance of pathogenic variants (PVs) represents a major challenge to the field of human genetics, often complicating clinical decision-making and risk management. Nonpenetrance, the detection of PVs in the absence of disease manifestation, is a common phenomenon, yet, we know very little about the underlying factors, which may protect some individuals and not others. Placing a new focus on the genomic study of the healthy elderly may be pivotal for advancing our understanding of penetrance. Studying those who remain unaffected late into life, despite harboring known genetic risk variants, could provide important insights into disease mechanisms and ultimately inform clinical care, yet, it has received relatively little attention as a research strategy...
September 6, 2017: Genetic Testing and Molecular Biomarkers
https://www.readbyqxmd.com/read/28873450/bromide-supplementation-exacerbated-the-renal-dysfunction-injury-and-fibrosis-in-a-mouse-model-of-alport-syndrome
#7
Tsubasa Yokota, Kohei Omachi, Mary Ann Suico, Haruka Kojima, Misato Kamura, Keisuke Teramoto, Shota Kaseda, Jun Kuwazuru, Tsuyoshi Shuto, Hirofumi Kai
A seminal study recently demonstrated that bromide (Br-) has a critical function in the assembly of type IV collagen in basement membrane (BM), and suggested that Br- supplementation has therapeutic potential for BM diseases. Because salts of bromide (KBr and NaBr) have been used as antiepileptic drugs for several decades, repositioning of Br- for BM diseases is probable. However, the effects of Br- on glomerular basement membrane (GBM) disease such as Alport syndrome (AS) and its impact on the kidney are still unknown...
2017: PloS One
https://www.readbyqxmd.com/read/28871541/procedures-of-mitochondria-purification-and-gene-expression-to-study-alternative-respiratory-and-uncoupling-pathways-in-fruits
#8
Jurandi Gonçalves de Oliveira, Luis Miguel Mazorra Morales, Gláucia Michelle Cosme Silva, Kátia Daniella da Cruz Saraiva, Diederson Bortolino Santana, Clesivan Pereira Dos Santos, Marcos Goes Oliveira, José Hélio Costa
We describe detailed procedures to get intact and well-coupled mitochondria from a variety of fruit species such as papaya (Carica papaya), guava (Psidium guajava), tomato (Solanum lycopersicum), and strawberry (Fragaria x ananassa) as well as the protocols to assess the capacities of AOX and UCP pathways in intact fruit mitochondria. The procedures presented here were tested for the species mentioned above; their use with other types of fruits must be tested for yield of intact and active mitochondria. This is possible from individual adjustments...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28865492/pathobiology-of-the-129-stat1-mouse-model-of-human-age-related-er-positive-breast-cancer-with-an-immune-infiltrate-excluded-phenotype
#9
Hidetoshi Mori, Jane Q Chen, Robert D Cardiff, Zsófia Pénzváltó, Neil E Hubbard, Louis Schuetter, Russell C Hovey, Josephine F Trott, Alexander D Borowsky
BACKGROUND: Stat1 gene-targeted knockout mice (129S6/SvEvTac-Stat1 (tm1Rds)) develop estrogen receptor-positive (ER(+)), luminal-type mammary carcinomas at an advanced age. There is evidence for both host environment as well as tumor cell-intrinsic mechanisms to initiate tumorigenesis in this model. In this report, we summarize details of the systemic and mammary pathology at preneoplastic and tumor-bearing time points. In addition, we investigate tumor progression in the 129:Stat1 (-/-) host compared with wild-type 129/SvEv, and we describe the immune cell reaction to the tumors...
September 2, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28865372/impact-of-inoculum-sources-on-biotransformation-of-pharmaceuticals-and-personal-care-products
#10
Sunah Kim, Karen Rossmassler, Corey D Broeckling, Sarah Galloway, Jessica Prenni, Susan K De Long
Limited knowledge of optimal microbial community composition for PPCP biotreatment, and of the microbial phylotypes that drive biotransformation within mixed microbial communities, has hindered the rational design and operation of effective and reliable biological PPCP treatment technologies. Herein, bacterial community composition was investigated as an isolated variable within batch biofilm reactors via comparison of PPCP removals for three distinct inocula. Inocula pre-acclimated to model PPCPs were derived from activated sludge (AS), ditch sediment historically-impacted by wastewater treatment plant effluent (Sd), and material from laboratory-scale soil aquifer treatment (SAT) columns...
August 21, 2017: Water Research
https://www.readbyqxmd.com/read/28855065/predicting-72-hour-emergency-department-revisits
#11
Gene Pellerin, Kelly Gao, Laurence Kaminsky
OBJECTIVES: To develop a predictive model that hospitals or healthcare systems can use to identify patients at high risk of revisiting the ED within 72h so that appropriate interventions can be delivered. METHODS: This study employed multivariate logistic regression in developing the predictive model. The study data were from four Veterans medical centers in Upstate New York; 21,141 patients in total with ED visits were included in the analysis. Fiscal Year (FY) 2013 data were used to predict revisits in FY 2014...
August 25, 2017: American Journal of Emergency Medicine
https://www.readbyqxmd.com/read/28838317/applying-next-generation-sequencing-with-microdroplet-pcr-to-determine-the-disease-causing-mutations-in-retinal-dystrophies
#12
Xinjing Wang, Wadih M Zein, Leera D'Souza, Chimere Roberson, Keith Wetherby, Hong He, Angela Villarta, Amy Turriff, Kory R Johnson, Yang C Fann
BACKGROUND: Inherited Retinal dystrophy (IRD) is a broad group of inherited retinal disorders with heterogeneous genotypes and phenotypes. Next generation sequencing (NGS) methods have been broadly applied for analyzing patients with IRD. Here we report a novel approach to enrich the target gene panel by microdroplet PCR. METHODS: This assay involved a primer library which targeted 3071 amplicons from 2078 exons comprised of 184 genes involved in retinal function and/or retinal development...
August 24, 2017: BMC Ophthalmology
https://www.readbyqxmd.com/read/28832450/hla-population-genetics-in-solid-organ-transplantation
#13
Evan P Kransdorf, Marcelo J Pando, Loren Gragert, Bruce Kaplan
HLAs are fundamental to the adaptive immune response and play critical roles in the cellular and humoral response in solid organ transplantation. The genes encoding HLA proteins are the most polymorphic within the human genome, with thousands of different allelic variants known within the population. Application of the principles of population genetics to the HLA genes has resulted in the development of a numeric metric, the calculated panel-reactive antibody (CPRA) that predicts the likelihood of a positive crossmatch as a function of a transplant candidate's unacceptable HLA antigens...
September 2017: Transplantation
https://www.readbyqxmd.com/read/28815849/molecular-aspects-of-uterine-diseases-in-dogs
#14
REVIEW
R Hagman
Uterine diseases are common in dogs, particularly in countries where elective spaying is not usually performed. The associated clinical illnesses may be of varying degree ranging from merely decreased fertility to a critical pyometra requiring intensive care to survive. The diagnosis of some uterine diseases is generally uncomplicated, such as in a classic pyometra presenting with enlarged, fluid-filled uterus, purulent vaginal discharge and characteristic signs of illness or in other disorders associated with uterine enlargement...
August 2017: Reproduction in Domestic Animals, Zuchthygiene
https://www.readbyqxmd.com/read/28803549/comparative-gut-microbiota-and-resistome-profiling-of-intensive-care-patients-receiving-selective-digestive-tract-decontamination-and-healthy-subjects
#15
Elena Buelow, Teresita D J Bello González, Susana Fuentes, Wouter A A de Steenhuijsen Piters, Leo Lahti, Jumamurat R Bayjanov, Eline A M Majoor, Johanna C Braat, Maaike S M van Mourik, Evelien A N Oostdijk, Rob J L Willems, Marc J M Bonten, Mark W J van Passel, Hauke Smidt, Willem van Schaik
BACKGROUND: The gut microbiota is a reservoir of opportunistic pathogens that can cause life-threatening infections in critically ill patients during their stay in an intensive care unit (ICU). To suppress gut colonization with opportunistic pathogens, a prophylactic antibiotic regimen, termed "selective decontamination of the digestive tract" (SDD), is used in some countries where it improves clinical outcome in ICU patients. Yet, the impact of ICU hospitalization and SDD on the gut microbiota remains largely unknown...
August 14, 2017: Microbiome
https://www.readbyqxmd.com/read/28793145/role-of-genetic-testing-in-inherited-cardiovascular-disease-a-review
#16
Allison L Cirino, Stephanie Harris, Neal K Lakdawala, Michelle Michels, Iacopo Olivotto, Sharlene M Day, Dominic J Abrams, Philippe Charron, Colleen Caleshu, Christopher Semsarian, Jodie Ingles, Harry Rakowski, Daniel P Judge, Carolyn Y Ho
Importance: Genetic testing is a valuable tool for managing inherited cardiovascular disease in patients and families, including hypertrophic, dilated, and arrhythmogenic cardiomyopathies and inherited arrhythmias. By identifying the molecular etiology of disease, genetic testing can improve diagnostic accuracy and refine family management. However, unique features associated with genetic testing affect the interpretation and application of results and differentiate it from traditional laboratory-based diagnostics...
August 9, 2017: JAMA Cardiology
https://www.readbyqxmd.com/read/28755059/nusinersen-the-first-option-beyond-supportive-care-for-spinal-muscular-atrophy
#17
REVIEW
Vikas Maharshi, Shazia Hasan
Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by degeneration of spinal motor neurons and poses significant adverse outcome in affected population. Survival motor neuron 1 (SMN1) protein encoded by SMN1 gene located on 5q(13) is critical for survival and functioning of motor neurons. Almost identical gene SMN2, present on the same chromosome, produces a small truncated protein (SMN2) because of skipping of exon 7 from translation due to translation silent C6U substitution in exon 7 of SMN2 pre-mRNA transcript...
July 28, 2017: Clinical Drug Investigation
https://www.readbyqxmd.com/read/28754681/nitric-oxide-modulates-macrophage-responses-to-mycobacterium-tuberculosis-infection-through-activation-of-hif-1%C3%AE-and-repression-of-nf-%C3%AE%C2%BAb
#18
Jonathan Braverman, Sarah A Stanley
IFN-γ is essential for control of Mycobacterium tuberculosis infection in vitro and in vivo. However, the mechanisms by which IFN-γ controls infection remain only partially understood. One of the crucial IFN-γ target genes required for control of M. tuberculosis is inducible NO synthase (iNOS). Although NO produced by iNOS is thought to have direct bactericidal activity against M. tuberculosis, the role of NO as a signaling molecule has been poorly characterized in the context M. tuberculosis infection. In this study, we found that iNOS broadly regulates the macrophage transcriptome during M...
September 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28751446/gene-copy-number-estimation-from-targeted-next-generation-sequencing-of-prostate-cancer-biopsies-analytic-validation-and-clinical-qualification
#19
George Seed, Wei Yuan, Joaquin Mateo, Suzanne Carreira, Claudia Bertan, Maryou Lambros, Gunther Boysen, Roberta Ferraldeschi, Susana Miranda, Ines Figueiredo, Ruth Riisnaes, Mateus Crespo, Daniel Nava Rodrigues, Eric Talevich, Dan R Robinson, Lakshmi P Kunju, Yi-Mi Wu, Robert Lonigro, Shahneen Sandhu, Arul Chinnayan, Johann S de Bono
Abstract <p>Purpose</p> <p>Precise detection of copy number aberrations (CNAs) from tumor biopsies is critically important to the treatment of metastatic prostate cancer. The use of targeted panel next generation sequencing (NGS) is inexpensive, high throughput and easily feasible, allowing single nucleotide variant calls, but CNA estimation from this remains challenging..</p> <p>Experimental Design</p> <p>We evaluated CNVkit for CNA identification from amplicon-based targeted NGS in a cohort of 110 fresh castration resistant prostate cancer biopsies, and used capture based whole exome sequencing (WES), array comparative genomic hybridization (aCGH), and fluorescent in situ hybridization (FISH) to explore the viability of this approach...
July 27, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28750088/a-single-nucleotide-polymorphism-causes-enhanced-radical-oxygen-species-production-by-human-aldehyde-oxidase
#20
Alessandro Foti, Frank Dorendorf, Silke Leimkühler
Aldehyde oxidases (AOXs) are molybdo-flavoenzymes characterized by broad substrate specificity, oxidizing aromatic/aliphatic aldehydes into the corresponding carboxylic acids and hydroxylating various heteroaromatic rings. The enzymes use oxygen as the terminal electron acceptor and produce reduced oxygen species during turnover. The physiological function of mammalian AOX isoenzymes is still unclear, however, human AOX (hAOX1) is an emerging enzyme in phase-I drug metabolism. Indeed, the number of xenobiotics acting as hAOX1 substrates is increasing...
2017: PloS One
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