Purpose
To determine how much money could potentially be saved by re-evaluating a patient’s prior recent abdominal CT for lumbar spine pathology instead of ordering a lumbar spine MRI.
Methods
...Abdominal CT studies, from all consecutive patients who had an abdominal CT within 12 months prior to a lumbar spine MRI obtained between 11/1/15 and 5/30/16, were retrospectively reviewed in a blinded fashion for the presence of any significant lumbar spine abnormalities. CT studies that accurately reflected all normal and abnormal findings when compared to the standard of reference, the prospectively interpreted lumbar spine MR imaging reports, were used to indicate which lumbar spine MRI studies potentially could have been avoided and to calculate the potential cost savings.
Results
Of the 81 abdominal CT studies that met the inclusion criteria of this study, 62% (50/81) were TP, 28% (23/81) were TN, 5% (4/81) were FP, and 5% (4/81) were FN studies. 90% (73/81) of the lumbar spine MRI studies could potentially have been avoided during the 7 months of this study. The predicted savings by reviewing the abdominal CT for lumbar spine abnormalities prior to ordering a lumbar spine MRI are an estimated 1.2–3.4 billion dollars per year.
Conclusion
Recent abdominal CT studies should be reviewed for lumbar spine pathology prior to a patient undergoing lumbar spine MRI. Avoiding unnecessary lumbar spine MRI studies could potentially save the U.S. healthcare system an estimated 1.2–3.4 billion dollars per year.
Liver fibrosis (LF) leads to liver failure and short survival. Liver glycogen is a hyperbranched glucose polymer, comprising individual β particles, which can bind together to form aggregated α ...particles. Glycogen functionality depends on its molecular structure. This study compared the molecular structure of liver glycogen from both LF and healthy rats, and explored underlying mechanisms for observed differences. Glycogen from both groups contained α and β particles; the LF group contained a higher proportion of β particles, with the glycogen containing fewer long chains than seen in the control group. Both glycogen branching enzyme and glycogen phosphorylase showed a significant decrease of activity in the LF group. Transcriptomics and proteomics revealed a functional deficiency of mitochondria in the LF group, which may lead to changes in glycogen structure. These results provide for the first time an understanding of how liver fibrosis affects liver glycogen metabolism and glycogen structure.
We hypothesized that the molecular structure of liver glycogen from a rat model of liver fibrosis would be altered compared to the control group.
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•Liver fibrosis affects glycogen metabolism.•Liver fibrosis alters the molecular structure of liver glycogen.•Glycogen structure affects its properties.•Liver fibrosis causes a functional deficiency of mitochondria.•Mitochondrial function may affect glycogen molecular structure.
Cancer vaccines may be harnessed to incite immunity against poorly immunogenic tumors, however they have failed in therapeutic settings. Poor antigenicity coupled with systemic and intratumoral ...immune suppression have been significant drawbacks. RNA encoding for tumor associated or specific epitopes can serve as a more immunogenic and expeditious trigger of anti-tumor immunity. RNA stimulates innate immunity through toll like receptor stimulation producing type I interferon, and it mediates potent adaptive responses. Since RNA is inherently unstable, delivery systems have been developed to protect and deliver it to intended targets in vivo. In this review, we discuss liposomes as RNA delivery vehicles and their role as cancer vaccines.
Use of topiramate in pregnancy and risk of oral clefts Margulis, Andrea V., MD, ScD; Mitchell, Allen A., MD; Gilboa, Suzanne M., PhD ...
American journal of obstetrics and gynecology,
11/2012, Volume:
207, Issue:
5
Journal Article
Peer reviewed
Open access
Objective The objective of this study was to evaluate the association between the use of monotherapy topiramate in pregnancy and cleft lip with or without cleft palate (CL/P) in the offspring. Study ...Design Data from the Slone Epidemiology Center Birth Defects Study (BDS) from 1997 to 2009 and the National Birth Defects Prevention Study (NBDPS) from 1997 to 2007 were analyzed. Conditional logistic regression was used to compare the first-trimester use of topiramate monotherapy to no antiepileptic drug use during the periconceptional period between the mothers of infants with CL/P and the mothers of controls for each study separately and in pooled data. Results The BDS contained 785 CL/P cases and 6986 controls; the NBDPS contained 2283 CL/P cases and 8494 controls. The odds ratios (exact 95% confidence intervals) for the association between topiramate use and CL/P were 10.1 (1.1-129.2) in the BDS, 3.6 (0.7-20.0) in the NBDPS, and 5.4 (1.5-20.1) in the pooled data. Conclusion First-trimester use of topiramate may be associated with CL/P.
SCRaMbLE (Synthetic Chromosome Rearrangement and Modification by LoxP-mediated Evolution) is a genome restructuring technique that can be used in synthetic genomes such as that of Sc2.0, the ...synthetic yeast genome, which contains hundreds to thousands of strategically positioned loxPsym sites. SCRaMbLE has been used to induce rearrangements in yeast strains harboring one or more synthetic chromosomes, as well as plasmid DNA in vitro and in vivo. Here we describe a collection of heterozygous diploid strains produced by mating haploid semisynthetic Sc2.0 strains to haploid native parental strains. We subsequently demonstrate that such heterozygous diploid strains are more robust to the effects of SCRaMbLE than haploid semisynthetic strains, rapidly improve rationally selected phenotypes in SCRaMbLEd heterozygous diploids, and establish that multiple sets of independent genomic rearrangements are able to lead to similar phenotype enhancements. Finally, we show that heterozygous diploid SCRaMbLE can also be carried out in interspecies hybrid strains.
In the United States the rate of stillbirth after 28 weeks' gestation (late stillbirth) is 2.7/1000 births. Fetuses that are small for gestational age (SGA) or large for gestational age (LGA) are at ...increased risk of stillbirth. SGA and LGA are often categorized as growth or birthweight ≤ 10th and ≥ 90th centile, respectively; however, these cut-offs are arbitrary. We sought to characterize the relationship between birthweight and stillbirth risk in greater detail. Data on singleton births between 28- and 44-weeks' gestation from 2014 to 2015 were extracted from the US Centers for Disease Control and Prevention live birth and fetal death files. Growth was assessed using customized birthweight centiles (Gestation Related Optimal Weight; GROW). The analyses included logistic regression using SGA/LGA categories and a generalized additive model (GAM) using birthweight centile as a continuous exposure. Although the SGA and LGA categories identified infants at risk of stillbirth, categorical models provided poor fits to the data within the high-risk bins, and in particular markedly underestimated the risk for the extreme centiles. For example, for fetuses in the lowest GROW centile, the observed rate was 39.8/1000 births compared with a predicted rate of 11.7/1000 from the category-based analysis. In contrast, the model-predicted risk from the GAM tracked closely with the observed risk, with the GAM providing an accurate characterization of stillbirth risk across the entire birthweight continuum. This study provides stillbirth risk estimates for each GROW centile, which clinicians can use in conjunction with other clinical details to guide obstetric management.
Our laboratory previously determined that vitamin D3, the vitamin D receptor (VDR), and 1α hydroxylase are present and active in the eye. In this study, we examined the effects of VDR knockout on ...wound healing, the tight junction-associated proteins occludin and ZO-1, and tight junction numbers in mouse corneas.
Epithelial wounds (2-mm) were made with an agar brush on 4-week-old and 10-week-old wild-type, heterozygous, and VDR knockout mouse corneas. Mice were on a normal or high lactose, Ca(2+), and PO₄(-) diet. Wound-healing area was measured over time. Real-time PCR was used to quantify occludin and ZO-1 message expression. Western blot was used for protein expression. Transmission electron microscopy was used to examine corneal epithelium and endothelium tight junctions. Immunofluorescence was used to examine epithelial ZO-1 distribution.
Results showed a decreased healing rate in 10-week-old VDR knockout mice compared with wild-types. Vitamin D receptor knockout mice on the special diet had no difference in healing rate compared with wild-types. Real-time PCR showed decreased expression of occludin and ZO-1 in 10-week-old VDR knockout mice compared with wild-types. Western blot of 10-week-old knockout mouse corneas showed decreased occludin expression compared with wild-types. Transmission electron microscopy showed a significant difference in tight junction numbers in VDR knockouts versus wild-types. Immunofluorescence showed a change in ZO-1 distribution among genotypes.
Vitamin D receptor knockout affects mouse corneal epithelium wound healing and tight junction integrity.
Interferon (IFN) is widely recognised to be an integral part of the innate immune response to viral infection. Since its initial discovery in 1957 by Isaacs and Lindenmann, various IFN sub-types have ...been identified and there are now three distinct classes recognised-Type I (IFN-α and IFN-β), Type II (IFN-γ) and Type III (IFN-λ), distinguished by their differing receptors. As well as displaying profound antiviral activity in vivo, IFN has anti-proliferative, cytotoxic and anti-tumoural roles. In an attempt to harness their immunomodulatory potential, investigators and clinicians have investigated the use of IFNs for the treatment of human diseases with considerable success. For example, IFN-α preparations are now a critical component in the treatment of chronic Hepatitis C infection and IFN-β therapy is now the first line treatment for relapsing remitting multiple sclerosis. However, IFN therapy is also associated with significant morbidity and in some patients is poorly tolerated. In this review, we explore the scientific basis for IFN therapy and outline its therapeutic scope. We describe the commonly encountered side effects and attempt to explain the less well recognised pulmonary complications including emerging evidence of life threatening and irreversible pulmonary vascular pathology. Finally, we look to the future of interferon drug treatment, examining the potential for emerging therapies.
Rhythmic changes in histone acetylation at circadian clock genes suggest that temporal modulation of gene expression is regulated by chromatin modifications. Furthermore, recent studies demonstrate a ...critical relationship between circadian and metabolic physiology. The nuclear receptor corepressor 1 (Ncor1) functions as an activating subunit for the chromatin modifying enzyme histone deacetylase 3 (Hdac3). Lack of Ncor1 is incompatible with life, and hence it is unknown whether Ncor1, and particularly its regulation of Hdac3, is critical for adult mammalian physiology. Here we show that specific, genetic disruption of the Ncor1-Hdac3 interaction in mice causes aberrant regulation of clock genes and results in abnormal circadian behaviour. These mice are also leaner and more insulin-sensitive owing to increased energy expenditure. Unexpectedly, loss of a functional Ncor1-Hdac3 complex in vivo does not lead to sustained increases in known catabolic genes, but instead significantly alters the oscillatory patterns of several metabolic genes, demonstrating that circadian regulation of metabolism is critical for normal energy balance. These findings indicate that activation of Hdac3 by Ncor1 is a nodal point in the epigenetic regulation of circadian and metabolic physiology.
This study reports comprehensive clinical pathology data for hematology, serum, and plasma biochemistry reference intervals for 174 apparently healthy common bottlenose dolphins (
Tursiops truncatus
...) and reference values for 27 Indo-Pacific bottlenose dolphins (
Tursiops aduncus
), 13 beluga whales (
Delphinapterus leucas
), and 6 Pacific white-sided dolphins (
Lagenorhynchus obliquidens
) in zoos and aquariums accredited by the Alliance for Marine Mammal Parks and Aquariums and the Association of Zoos & Aquariums. Blood samples were collected as part of a larger study titled “Towards understanding the welfare of cetaceans in zoos and aquariums” (colloquially called the Cetacean Welfare Study). Two blood samples were collected following a standardized protocol, and two veterinarian examinations were conducted approximately six months apart between July to November 2018 and January to April 2019. Least square means, standard deviations, and 95% confidence intervals were calculated for hematology, serum, and plasma biochemical variables. Comparisons by age, gender, and month revealed statistically significant differences (
p
< 0.01) for several variables. Reference intervals and values were generated for samples tested at two laboratories for up to 56 hematologic, serum, and plasma biochemical variables. To apply these data, ZooPhysioTrak, an iOS mobile software application, was developed to provide a new resource for cetacean management. ZooPhysioTrak provides species-specific reference intervals and values based on user inputs of individual demographic and sample information. These data provide a baseline from which to compare hematological, serum, and plasma biochemical values in cetaceans in zoos and aquariums.
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