Laboratory tests in patients treated with isotretinoin: occurrence of liver and muscle abnormalities and failure of AST and ALT to predict liver abnormality.

Current laboratory monitoring may not be optimal. A retrospective chart review was performed on thelaboratory results of 246 patients who were treated with isotretinoin for acne over a 9-year period. Tests obtained were CBC, lipid panel, AST, ALT, CK, GGT,and C-reactive protein. Thirty-five patients had an elevated AST and 35 of these had an elevated CK; 32 had an elevated ALT and 11 of these had an elevated CK. Thirteen patients had an elevated GGT; in 5 this was the only abnormality, whereas 8 had a GGT elevation accompanied by an elevated AST or ALT. Two had an elevated GGT and an elevated CK with normal AST and ALT. Fifty-two patients had a single episode of elevated CK, of which 22 were female. However, 57 had multiple CK elevations and only one was female. Thirty-five patients had CK elevationsnormal; 38 had levels between 2 and 3 times normal, 18 had levels between 3 and 4 times normal, and 18 had levels greater than 4 times normal. We suggest that ALT and AST are not useful for monitoring isotretinoin therapy and that GGT and CK may be of greater value in managing patients

Portraits of people with dementia : three case studies of creating portraits

Peer reviewedPreprin

Pigment Dispersing Factors and Their Cognate Receptors in a Crustacean Model, With New Insights Into Distinct Neurons and Their Functions

Pigment dispersing factors (PDFs, or PDHs in crustaceans) form a structurally related group of neuropeptides found throughout the Ecdysozoa and were first discovered as pigmentary effector hormones in crustaceans. In insects PDFs fulfill crucial neuromodulatory roles, most notably as output regulators of the circadian system, underscoring their central position in physiological and behavioral organization of arthropods. Intriguingly, decapod crustaceans express multiple isoforms of PDH originating from separate genes, yet their differential functions are still to be determined. Here, we functionally define two PDH receptors in the crab Carcinus maenas and show them to be selectively activated by four PDH isoforms: PDHR 43673 was activated by PDH-1 and PDH-2 at low nanomolar doses whilst PDHR 41189 was activated by PDH-3 and an extended 20 residue e-PDH. Detailed examination of the anatomical distribution of all four peptides and their cognate receptors indicate that they likely perform different functions as secreted hormones and/or neuromodulators, with PDH-1 and its receptor 43,673 implicated in an authentic hormonal axis. PDH-2, PDH-3, and e-PDH were limited to non-neurohemal interneuronal sites in the CNS; PDHR 41189 was largely restricted to the nervous system suggesting a neuromodulatory function. Notably PDH-3 and e-PDH were without chromatophore dispersing activity. This is the first report which functionally defines a PDHR in an endocrine system in a crustacean and to indicate this and other putative roles of this physiologically pivotal peptide group in these organisms. Thus, our findings present opportunities to further examine the endocrine and circadian machinery in this important arthropod phylum

Predicting Bone Mechanical Properties of Cancellous Bone from DXA, MRI, and Fractal Dimensional Measurements

This project was aimed at making predictions of bone mechanical properties from non-invasive DXA and MRI measurements. Given the bone mechanical properties, stress calculations can be made to compare normal bone stresses to the stresses developed in exercise countermeasures against bone loss during space flight. These calculations in turn will be used to assess whether mechanical factors can explain bone loss in space. In this study we assessed the use of T2(sup *) MRI imaging, DXA, and fractal dimensional analysis to predict strength and stiffness in cancellous bone

Chemical and Photometric Evolution of Extended Ultraviolet Disks: Optical Spectroscopy of M83 (NGC5236) and NGC4625

We present the results from the analysis of optical spectra of 31 Halpha-selected regions in the extended UV (XUV) disks of M83 (NGC5236) and NGC4625 recently discovered by GALEX. The spectra were obtained using IMACS at Las Campanas Observatory 6.5m Magellan I telescope and COSMIC at the Palomar 200-inch telescope, respectively for M83 and NGC4625. The line ratios measured indicate nebular oxygen abundances (derived from the R23 parameter) of the order of Zsun/5-Zsun/10. For most emission-line regions analyzed the line fluxes and ratios measured are best reproduced by models of photoionization by single stars with masses in the range 20-40 Msun and oxygen abundances comparable to those derived from the R23 parameter. We find indications for a relatively high N/O abundance ratio in the XUV disk of M83. Although the metallicities derived imply that these are not the first stars formed in the XUV disks, such a level of enrichment could be reached in young spiral disks only 1 Gyr after these first stars would have formed. The amount of gas in the XUV disks allow maintaining the current level of star formation for at least a few Gyr.Comment: 52 pages, 8 tables, 7 figures, accepted for publication in Ap

Complete mitochondrial genomes and nuclear ribosomal RNA operons of two species of Diplostomum (Platyhelminthes: Trematoda): a molecular resource for taxonomy and molecular epidemiology of important fish pathogens

© 2015 Brabec et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http:// creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. The attached file is the published version of the article

Novel epigenetic network biomarkers for early detection of esophageal cancer

BACKGROUND: Early detection of esophageal cancer is critical to improve survival. Whilst studies have identified biomarkers, their interpretation and validity is often confounded by cell-type heterogeneity. RESULTS: Here we applied systems-epigenomic and cell-type deconvolution algorithms to a discovery set encompassing RNA-Seq and DNA methylation data from esophageal adenocarcinoma (EAC) patients and matched normal-adjacent tissue, in order to identify robust biomarkers, free from the confounding effect posed by cell-type heterogeneity. We identify 12 gene-modules that are epigenetically deregulated in EAC, and are able to validate all 12 modules in 4 independent EAC cohorts. We demonstrate that the epigenetic deregulation is present in the epithelial compartment of EAC-tissue. Using single-cell RNA-Seq data we show that one of these modules, a proto-cadherin module centered around CTNND2, is inactivated in Barrett's Esophagus, a precursor lesion to EAC. By measuring DNA methylation in saliva from EAC cases and controls, we identify a chemokine module centered around CCL20, whose methylation patterns in saliva correlate with EAC status. CONCLUSIONS: Given our observations that a CCL20 chemokine network is overactivated in EAC tissue and saliva from EAC patients, and that in independent studies CCL20 has been found to be overactivated in EAC tissue infected with the bacterium F. nucleatum, a bacterium that normally inhabits the oral cavity, our results highlight the possibility of using DNAm measurements in saliva as a proxy for changes occurring in the esophageal epithelium. Both the CTNND2/CCL20 modules represent novel promising network biomarkers for EAC that merit further investigation

Causes, patterns and severity of androgen excess in 487 consecutively recruited pre- and post-pubertal children

Objective Androgen excess in childhood is a common presentation and may signify sinister underlying pathology. Data describing its patterns and severity are scarce, limiting the information available for clinical decision processes. Here, we examined the differential diagnostic value of serum DHEAS, androstenedione (A4) and testosterone in childhood androgen excess. Design Retrospective review of all children undergoing serum androgen measurement at a single center over 5 years. Methods Serum A4 and testosterone were measured by tandem mass spectrometry and DHEAS by immunoassay. Patients with at least one increased androgen underwent phenotyping by clinical notes review. Results In 487 children with simultaneous DHEAS, A4 and testosterone measurements, we identified 199 with androgen excess (140 pre- and 59 post-pubertal). Premature adrenarche (PA) was the most common pre-pubertal diagnosis (61%), characterized by DHEAS excess in 85%, while A4 and testosterone were only increased in 26 and 9% respectively. PCOS was diagnosed in 40% of post-pubertal subjects, presenting equally frequent with isolated excess of DHEAS (29%) or testosterone (25%) or increases in both A4 and testosterone (25%). CAH patients (6%) predominantly had A4 excess (86%); testosterone and DHEAS were increased in 50 and 33% respectively. Concentrations increased above the two-fold upper limit of normal were mostly observed in PA for serum DHEAS (&gt;20-fold in the single case of adrenocortical carcinoma) and in CAH for serum androstenedione. Conclusions Patterns and severity of childhood androgen excess provide pointers to the underlying diagnosis and can be used to guide further investigations.</p

Seasonal Variations in Atmospheric Composition as Measured in Gale Crater, Mars

All MSL data used in this manuscript (REMS and SAM) are freely available on NASA's Planetary Data System (PDS) Geosciences Node, from within 6 months after receipt on Earth (http://pds‐geosciences.wustl.edu/missions/msl/). The mixing ratios developed and presented in this paper are available at a publicly available archive (dataverse.org: doi.org/10.7910/DVN/CVUOWW) as cited within the manuscript. The successful operation of the Curiosity rover and the SAM instrument on Mars is due to the hard work and dedication of hundreds of scientists, engineers, and managers over more than a decade. Essential contributions to the successful operation of SAM on Mars and the acquisition of SAM data were provided by the SAM development, operations, and test bed teams. The authors gratefully thank the SAM and MSL teams that have contributed in numerous ways to obtain the data that enabled this scientific work. We also thank NASA for the support of the development of SAM, SAM data analysis, and the continued support of the Mars Science Laboratory mission. The contribution of F. Lefèvre was supported by the Programme National de Planétologie (PNP). R. Navarro‐Gonzalez acknowledges support from the Universidad Nacional Autónoma de México (PAPIIT IN111619). LPI is operated by USRA under a cooperative agreement with the Science Mission Directorate of the National Aeronautics and Space Administration. We thank members of the SAM and larger MSL team for insightful discussions and support. In particular, we thank R. Becker and R. O. Pepin for careful review of data analysis and interpretation. We thank M. D. Smith for discussion of CRISM CO measurements. We thank A. Brunner, M. Johnson, and M. Lefavor for their development of customized data analysis tools used here and in other SAM publications.Peer reviewedPublisher PD

Ecosystem Interactions Underlie the Spread of Avian Influenza A Viruses with Pandemic Potential

Despite evidence for avian influenza A virus (AIV) transmission between wild and domestic ecosystems, the roles of bird migration and poultry trade in the spread of viruses remain enigmatic. In this study, we integrate ecosystem interactions into a phylogeographic model to assess the contribution of wild and domestic hosts to AIV distribution and persistence. Analysis of globally sampled AIV datasets shows frequent two-way transmission between wild and domestic ecosystems. In general, viral flow from domestic to wild bird populations was restricted to within a geographic region. In contrast, spillover from wild to domestic populations occurred both within and between regions. Wild birds mediated long-distance dispersal at intercontinental scales whereas viral spread among poultry populations was a major driver of regional spread. Viral spread between poultry flocks frequently originated from persistent lineages circulating in regions of intensive poultry production. Our analysis of long-term surveillance data demonstrates that meaningful insights can be inferred from integrating ecosystem into phylogeographic reconstructions that may be consequential for pandemic preparedness and livestock protection.National Institutes of Health (U.S.) (NIH Centers for Excellence in Influenza Research and Surveillance (CEIRS, contract # HHSN266200700010C))National Institutes of Health (U.S.) (NIH Centers for Excellence in Influenza Research and Surveillance (CEIRS, contract # HHSN272201400008C))National Institutes of Health (U.S.) (NIH Centers for Excellence in Influenza Research and Surveillance (CEIRS, contract # HHSN272201400006C)