Systemic reduction in glutathione levels occurs in patients with primary open-angle glaucoma

PURPOSE. To assess the level of plasma glutathione in patients with untreated primary open-angle glaucoma. METHODS. Twenty-one patients with newly diagnosed primary open-angle glaucoma and 34 age- and gender-matched control subjects were subjected to a blood analysis to detect the level of circulating glutathione in its reduced and oxidized forms. The effect of age, gender, and systemic blood pressure on circulating glutathione levels was also analyzed. RESULTS. Age had a negative effect on the level of both reduced and total glutathione (P = 0.002, r = -0.52 and P = 0.002, r = -0.52, respectively) in control subjects but not in patients with glaucoma (P > 0.05, r = 0.27, and P > 0.05, r = 0.22, respectively). In the control group, men demonstrated higher levels of both reduced and total glutathione than did women (P = 0.024 and P = 0.032, respectively). After correction for age and gender influences on blood glutathione levels, patients with glaucoma exhibited significantly lower levels of reduced and total glutathione than did control subjects (P = 0.010, F = 7.24 and P = 0.006, F = 8.38, respectively). No differences between study groups were observed in either oxidized glutathione levels or redox index (P > 0.05, F = 0.50; and P > 0.05, F = 0.30, respectively). CONCLUSIONS. Patients with glaucoma exhibit low levels of circulating glutathione, suggesting a general compromise of the antioxidative defense. Copyright © Association for Research in Vision and Ophthalmology

The Implications of M Dwarf Flares on the Detection and Characterization of Exoplanets at Infrared Wavelengths

We present the results of an observational campaign which obtained high time cadence, high precision, simultaneous optical and IR photometric observations of three M dwarf flare stars for 47 hours. The campaign was designed to characterize the behavior of energetic flare events, which routinely occur on M dwarfs, at IR wavelengths to milli-magnitude precision, and quantify to what extent such events might influence current and future efforts to detect and characterize extrasolar planets surrounding these stars. We detected and characterized four highly energetic optical flares having U-band total energies of ~7.8x10^30 to ~1.3x10^32 ergs, and found no corresponding response in the J, H, or Ks bandpasses at the precision of our data. For active dM3e stars, we find that a ~1.3x10^32 erg U-band flare (delta Umax ~1.5 mag) will induce <8.3 (J), <8.5 (H), and <11.7 (Ks) milli-mags of a response. A flare of this energy or greater should occur less than once per 18 hours. For active dM4.5e stars, we find that a ~5.1x10^31 erg U-band flare (delta Umax ~1.6 mag) will induce <7.8 (J), <8.8 (H), and <5.1 (Ks) milli-mags of a response. A flare of this energy or greater should occur less than once per 10 hours. No evidence of stellar variability not associated with discrete flare events was observed at the level of ~3.9 milli-mags over 1 hour time-scales and at the level of ~5.6 milli-mags over 7.5 hour time-scales. We therefore demonstrate that most M dwarf stellar activity and flares will not influence IR detection and characterization studies of M dwarf exoplanets above the level of ~5-11 milli-mags, depending on the filter and spectral type. We speculate that the most energetic megaflares on M dwarfs, which occur at rates of once per month, are likely to be easily detected in IR observations with sensitivity of tens of milli-mags.Comment: Accepted in Astronomical Journal, 17 pages, 6 figure

Efforts at the Frontlines: Implementing a Hepatitis C Testing and Linkage-to-Care Program at the Local Public Health Level

The national Viral Hepatitis Action Plan recommends strengthening partnerships among health departments, community-based organizations, and health-care providers for hepatitis services. We implemented a hepatitis C virus (HCV) testing and linkage-to-care program through a local health department using similar strategies reported for HIV care

A Mouse Model of Harlequin Ichthyosis Delineates a Key Role for Abca12 in Lipid Homeostasis

Harlequin Ichthyosis (HI) is a severe and often lethal hyperkeratotic skin disease caused by mutations in the ABCA12 transport protein. In keratinocytes, ABCA12 is thought to regulate the transfer of lipids into small intracellular trafficking vesicles known as lamellar bodies. However, the nature and scope of this regulation remains unclear. As part of an original recessive mouse ENU mutagenesis screen, we have identified and characterised an animal model of HI and showed that it displays many of the hallmarks of the disease including hyperkeratosis, loss of barrier function, and defects in lipid homeostasis. We have used this model to follow disease progression in utero and present evidence that loss of Abca12 function leads to premature differentiation of basal keratinocytes. A comprehensive analysis of lipid levels in mutant epidermis demonstrated profound defects in lipid homeostasis, illustrating for the first time the extent to which Abca12 plays a pivotal role in maintaining lipid balance in the skin. To further investigate the scope of Abca12's activity, we have utilised cells from the mutant mouse to ascribe direct transport functions to the protein and, in doing so, we demonstrate activities independent of its role in lamellar body function. These cells have severely impaired lipid efflux leading to intracellular accumulation of neutral lipids. Furthermore, we identify Abca12 as a mediator of Abca1-regulated cellular cholesterol efflux, a finding that may have significant implications for other diseases of lipid metabolism and homeostasis, including atherosclerosis

Multi-wavelength Characterization of Stellar Flares on Low-mass Stars using SDSS and 2MASS Time Domain Surveys

We present the first rates of flares from M dwarf stars in both red optical and near-infrared (NIR) filters. We have studied ~50,000 M dwarfs from the Sloan Digital Sky Survey (SDSS) Stripe 82 area and 1321 M dwarfs from the Two Micron All Sky Survey (2MASS) Calibration Scan Point Source Working Database that overlap SDSS imaging fields. We assign photometric spectral types from M0 to M6 using (r – i) and (i – z) colors for every star in our sample. Stripe 82 stars each have 50-100 epochs of data, while 2MASS Calibration stars have ~1900 epochs. From these data we estimate the observed rates and theoretical detection thresholds for flares in eight photometric bands as a function of spectral type. Optical flare rates are found to be in agreement with previous studies, while the frequency per hour of NIR flare detections is found to be more than two orders of magnitude lower. An excess of small-amplitude flux increases in all bands exhibits a power-law distribution, which we interpret as the result of flares below our detection thresholds. In order to investigate the recovery efficiency for flares in each filter, we extend a two-component flare model into the NIR. Quiescent M0-M6 spectral templates were used with the model to predict the photometric response of flares from u to Ks . We determine that red optical filters are sensitive to flares with u-band amplitudes 2 mag, and NIR filters to flares with Δu 4.5 mag. Our model predicts that M0 stars have the best color contrast for J-band detections, but M4-M6 stars should yield the highest rate of NIR flares with amplitudes of ΔJ ≥ 0.01 mag. Characterizing flare rates and photometric variations at longer wavelengths is important for predicting the signatures of M dwarf variability in next-generation surveys, and we discuss their impact on surveys such as the Large Synoptic Survey Telescope

Deficiency of the zinc finger protein ZFP106 causes motor and sensory neurodegeneration

Acknowledgements We are indebted to Jim Humphries, JennyCorrigan, LizDarley, Elizabeth Joynson, Natalie Walters, Sara Wells and the whole necropsy, histology, genotyping and MLC ward 6 teams at MRC Harwell for excellent technical assistance. We thank the staff of the WTSI Illumina Bespoke Team for the RNA-seq data, the Sanger Mouse Genetics Project for the initial mouse characterization and Dr David Adams for critical reading of the manuscript. We also thank KOMP for the mouse embryonic stem cells carrying the knockout first promoter-less allele (tm1a(KOMP)Wtsi) within Zfp016. Conflict of Interest statement. None declared. Funding This work was funded by the UK Medical Research Council (MRC) to A.A.-A. and a Motor Neurone Disease Association (MNDA) project grant to A.A.-A. and EMCF. D.L.H.B. is a Wellcome Trust Senior Clinical Scientist Fellow and P.F. is a MRC/MNDA Lady Edith Wolfson Clinician Scientist Fellow. Funding to pay the Open Access publication charges for this article was provided by the MRC grant number: MC_UP_A390_1106.Peer reviewedPublisher PD

Gaps in detailed knowledge of human papillomavirus (HPV) and the HPV vaccine among medical students in Scotland

&lt;p&gt;Background: A vaccination programme targeted against human papillomavirus (HPV) types16 and 18 was introduced in the UK in 2008, with the aim of decreasing incidence of cervical disease. Vaccine roll out to 12–13 year old girls with a catch-up programme for girls aged up to 17 years and 364 days was accompanied by a very comprehensive public health information (PHI) campaign which described the role of HPV in the development of cervical cancer.&lt;/p&gt; &lt;p&gt;Methods: A brief questionnaire, designed to assess acquisition of knowledge of HPV infection and its association to cervical cancer, was administered to two different cohorts of male and female 1st year medical students (school leavers: 83% in age range 17–20) at a UK university. The study was timed so that the first survey in 2008 immediately followed a summer's intensive PHI campaign and very shortly after vaccine roll-out (150 students). The second survey was exactly one year later over which time there was a sustained PHI campaign (213 students).&lt;/p&gt; &lt;p&gt;Results: We addressed three research questions: knowledge about three specific details of HPV infection that could be acquired from PHI, whether length of the PHI campaign and/or vaccination of females had any bearing on HPV knowledge, and knowledge differences between men and women regarding HPV. No female student in the 2008 cohort had completed the three-dose vaccine schedule compared to 58.4% of female students in 2009. Overall, participants’ knowledge regarding the sexually transmitted nature of HPV and its association with cervical cancer was high in both year groups. However, in both years, less than 50% of students correctly identified that HPV causes over 90% of cases of cervical cancer. Males gave fewer correct answers for these two details in 2009. In 2008 only around 50% of students recognised that the current vaccine protects against a limited subset of cervical cancer-causing HPV sub-types, although there was a significant increase in correct response among female students in the 2009 cohort compared to the 2008 cohort.&lt;/p&gt; &lt;p&gt;onclusions: This study highlights a lack of understanding regarding the extent of protection against cervical cancer conferred by the HPV vaccine, even among an educated population in the UK who could have a vested interest in acquiring such knowledge. The intensive PHI campaign accompanying the first year of HPV vaccination seemed to have little effect on knowledge over time. This is one of the first studies to assess detailed knowledge of HPV in both males and females. There is scope for continued improvements to PHI regarding the link between HPV infection and cervical cancer.&lt;/p&gt

Metataxonomic and Metagenomic Approaches vs. Culture-Based Techniques for Clinical Pathology.

Diagnoses that are both timely and accurate are critically important for patients with life-threatening or drug resistant infections. Technological improvements in High-Throughput Sequencing (HTS) have led to its use in pathogen detection and its application in clinical diagnoses of infectious diseases. The present study compares two HTS methods, 16S rRNA marker gene sequencing (metataxonomics) and whole metagenomic shotgun sequencing (metagenomics), in their respective abilities to match the same diagnosis as traditional culture methods (culture inference) for patients with ventilator associated pneumonia (VAP). The metagenomic analysis was able to produce the same diagnosis as culture methods at the species-level for five of the six samples, while the metataxonomic analysis was only able to produce results with the same species-level identification as culture for two of the six samples. These results indicate that metagenomic analyses have the accuracy needed for a clinical diagnostic tool, but full integration in diagnostic protocols is contingent on technological improvements to decrease turnaround time and lower costs