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Kingsville TX 75965
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Loss of the RNA polymerase III repressor MAF1 confers obesity resistance. - Genes & development
MAF1 is a global repressor of RNA polymerase III transcription that regulates the expression of highly abundant noncoding RNAs in response to nutrient availability and cellular stress. Thus, MAF1 function is thought to be important for metabolic economy. Here we show that a whole-body knockout of Maf1 in mice confers resistance to diet-induced obesity and nonalcoholic fatty liver disease by reducing food intake and increasing metabolic inefficiency. Energy expenditure in Maf1(-/-) mice is increased by several mechanisms. Precursor tRNA synthesis was increased in multiple tissues without significant effects on mature tRNA levels, implying increased turnover in a futile tRNA cycle. Elevated futile cycling of hepatic lipids was also observed. Metabolite profiling of the liver and skeletal muscle revealed elevated levels of many amino acids and spermidine, which links the induction of autophagy in Maf1(-/-) mice with their extended life span. The increase in spermidine was accompanied by reduced levels of nicotinamide N-methyltransferase, which promotes polyamine synthesis, enables nicotinamide salvage to regenerate NAD(+), and is associated with obesity resistance. Consistent with this, NAD(+) levels were increased in muscle. The importance of MAF1 for metabolic economy reveals the potential for MAF1 modulators to protect against obesity and its harmful consequences.Â© 2015 Bonhoure et al.; Published by Cold Spring Harbor Laboratory Press.
PVNS or pseudo aneurysm: MRI-problem solving or misleading? - The Indian journal of radiology & imaging
Pigmented villonodular synovitis (PVNS) is a benign neoplastic process affecting the synovium. Magnetic resonance imaging (MRI) is considered as the imaging modality of choice, where PVNS is seen as a soft tissue lesion affecting the synovium with characteristic hypointense signal on T2-weighted images (T2WI) and typically blooming on gradient echo (GRE) sequences. MRI can sometimes be misleading, with many non-neoplastic pathologies having a tendency of recurrent bleeding closely mimicking PVNS. We report a caseâ€Š of pseudoaneurysm from posterior circumflex humeral artery, a branch of axillary artery, secondary to recurrent shoulder dislocation mimicking PVNS on MRI.
Ultrasound and Doppler features of Budd-Chiari syndrome in pediatric population. - Ultrasound quarterly
Budd-Chiari syndrome (BCS) occurs as a result of hepatic venous outflow obstruction. In the pediatric population, the etiologies vary as compared with the adult population. Decompensation can occur faster in this set of patients. Ultrasound and Doppler represent important imaging modalities for diagnosing BCS in children. The imaging features differ depending upon the level of obstruction, acuteness of the condition, and secondary decompensation. Caudate lobe hypertrophy is a salient feature. Obstruction at the level of hepatic veins may be manifested by ostial narrowing, echogenic thrombus, and altered flow patterns in the form of turbulent flow, nonvisualization of the veins, or reversal of flow. Obstruction in the inferior vena cava may present as an echogenic web, membrane, or thrombus with turbulent flow to absent flow within depending upon the degree of luminal compromise. Collateral formation is an important distinctive feature of subacute and chronic BCS. Collaterals that develop may be of intrahepatic or extrahepatic type. Secondary signs of liver failure would be present in late stages. Understanding the clinical presentation and imaging features can help in achieving the correct diagnosis because an early diagnosis of the disease will impact patient management.
How do students react to analyzing their own genomes in a whole-genome sequencing course?: outcomes of a longitudinal cohort study. - Genetics in medicine : official journal of the American College of Medical Genetics
Purpose:Health-care professionals need to be trained to work with whole-genome sequencing (WGS) in their practice. Our aim was to explore how students responded to a novel genome analysis course that included the option to analyze their own genomes.Methods:This was an observational cohort study. Questionnaires were administered before (T3) and after the genome analysis course (T4), as well as 6 months later (T5). In-depth interviews were conducted at T5.Results:All students (n = 19) opted to analyze their own genomes. At T5, 12 of 15 students stated that analyzing their own genomes had been useful. Ten reported they had applied their knowledge in the workplace. Technical WGS knowledge increased (mean of 63.8% at T3, mean of 72.5% at T4; P = 0.005). In-depth interviews suggested that analyzing their own genomes may increase students' motivation to learn and their understanding of the patient experience. Most (but not all) of the students reported low levels of WGS results-related distress and low levels of regret about their decision to analyze their own genomes.Conclusion:Giving students the option of analyzing their own genomes may increase motivation to learn, but some students may experience personal WGS results-related distress and regret. Additional evidence is required before considering incorporating optional personal genome analysis into medical education on a large scale.Genet Med advance online publication 29 January 2015Genetics in Medicine (2015); doi:10.1038/gim.2014.203.
An integrative pipeline for multi-modal discovery of disease relationships. - Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing
In the past decade there has been an explosion in genetic research that has resulted in the generation of enormous quantities of disease-related data. In the current study, we have compiled disease risk gene variant information and Electronic Medical Record (EMR) classification codes from various repositories for 305 diseases. Using such data, we developed a pipeline to test for clinical prevalence, gene-variant overlap, and literature presence for all 46,360 unique diseases pairs. To determine whether disease pairs were enriched we systematically employed both Fishers' Exact (medical and literature) and Term Frequency-Inverse Document Frequency (genetics) methodologies to test for enrichment, defining statistical significance at a Bonferonni adjusted threshold of (p < 1 Ã— 10(-6)) and weighted q < 0.05 accordingly. We hypothesize that disease pairs that are statistically enriched in medical and genetic spheres, but not so in the literature have the potential to reveal non-obvious connections between clinically disparate phenotypes. Using this pipeline, we identified 2,316 disease pairs that were significantly enriched within an EMR and 213 enriched genetically. Of these, 65 disease pairs were statistically enriched in both, 19 of which are believed to be novel. These identified non-obvious relationships between disease pairs are suggestive of a shared underlying etiology with clinical presentation. Further investigation of uncovered disease-pair relationships has the potential to provide insights into the architecture of complex diseases, and update existing knowledge of risk factors.
Hysterosalpingography and ultrasonography findings of female genital tuberculosis. - Diagnostic and interventional radiology (Ankara, Turkey)
Genital tuberculosis (TB) is an important cause of female infertility in the world, especially in developing countries. Majority of infertility cases are due to involvement of the fallopian tubes (92%-100%), endometrial cavity (50%), and ovaries (10%-30%); cervical and vulvovaginal TB are uncommon. Genital TB has characteristic radiological appearances based on the stage of the disease process (acute inflammatory or chronic fibrotic) and the organ of involvement. Hysterosalpingography (HSG) and ultrasonography (US) remain the main imaging modalities used in the diagnosis of genital TB. HSG is the primary modality for evaluating uterine, fallopian tube, and peritubal involvement and also helps in evaluating tubal patency. US, on the other hand, allows simultaneous evaluation of ovarian and extrapelvic involvement.
Comparison of split-dosing vs non-split (morning) dosing regimen for assessment of quality of bowel preparation for colonoscopy. - World journal of gastrointestinal endoscopy
To compare (using the Ottawa Bowel Preparation Scale) the efficacy of split-dose vs morning administration of polyethylene glycol solution for colon cleansing in patients undergoing colonoscopy, and to assess the optimal preparation-to-colonoscopy interval.Single-centre, prospective, randomized, investigator-blind stud in an academic tertiary-care centre. Two hundred patients requiring elective colonoscopy were assigned to receive one of the two preparation regimens (split vs morning) prior to colonoscopy. Main outcome measurements were bowel preparation quality and patient tolerability.Split-dose regimen resulted in better bowel preparation compared to morning regimen [Ottawa score mean 5.52 (SD 1.23) vs 6.02 (1.34); P = 0.017]. On subgroup analysis, for afternoon procedures, both the preparations were equally effective (P = 0.756). There was no difference in tolerability and compliance between the two regimens.Overall, previous evening - same morning split-dosing regimen results in better bowel cleansing for colonoscopy compared to morning preparation. For afternoon procedures, both schedules are equally effective; morning preparation may be more convenient to the patient.
Draft Genome Sequence of Bacillus alcalophilus AV1934, a Classic Alkaliphile Isolated from Human Feces in 1934. - Genome announcements
Bacillus alcalophilus AV1934, isolated from human feces, was described in 1934 before microbiome studies and recent indications of novel potassium ion coupling to motility in this extremophile. Here, we report draft sequences that will facilitate an examination of whether that coupling is part of a larger cycle of potassium ion-coupled transporters.Copyright Â© 2014 Attie et al.
Fatal nitrofurantoin lung. - The Journal of the Association of Physicians of India
Nitrofurantoin is a drug commonly used for urinary tract infections. It acts by damaging bacterial DNA. It is given in dose of 50-100 mg orally and is generally considered a safe drug but has occasionally been known to cause pulmonary toxicity which is usually reversible and only rarely fatal. We present a case of an elderly lady receiving nitrofurantoin for her urinary tract infection who developed sudden acute lung injury to which she finally succumbed within a few weeks.
Analytical validation of whole exome and whole genome sequencing for clinical applications. - BMC medical genomics
Whole exome and genome sequencing (WES/WGS) is now routinely offered as a clinical test by a growing number of laboratories. As part of the test design process each laboratory must determine the performance characteristics of the platform, test and informatics pipeline. This report documents one such characterization of WES/WGS.Whole exome and whole genome sequencing was performed on multiple technical replicates of five reference samples using the Illumina HiSeq 2000/2500. The sequencing data was processed with a GATK-based genome analysis pipeline to evaluate: intra-run, inter-run, inter-mode, inter-machine and inter-library consistency, concordance with orthogonal technologies (microarray, Sanger) and sensitivity and accuracy relative to known variant sets.Concordance to high-density microarrays consistently exceeds 97% (and typically exceeds 99%) and concordance between sequencing replicates also exceeds 97%, with no observable differences between different flow cells, runs, machines or modes. Sensitivity relative to high-density microarray variants exceeds 95%. In a detailed study of a 129 kb region, sensitivity was lower with some validated single-base insertions and deletions "not called". Different variants are "not called" in each replicate: of all variants identified in WES data from the NA12878 reference sample 74% of indels and 89% of SNVs were called in all seven replicates, in NA12878 WGS 52% of indels and 88% of SNVs were called in all six replicates. Key sources of non-uniformity are variance in depth of coverage, artifactual variants resulting from repetitive regions and larger structural variants.We report a comprehensive performance characterization of WES/WGS that will be relevant to offering laboratories, consumers of genome sequencing and others interested in the analytical validity of this technology.
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1310 General Cavzos Blvd. Kingsville, TX 75965
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4800 Ne Stallings Dr Suite 106
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