Proof of concept: A bioinformatic and serological screening method for identifying new peptide antigens for Chlamydia trachomatis related sequelae in women

This study aimed to identify new peptide antigens from Chlamydia (C.) trachomatis in a proof of concept approach which could be used to develop an epitope-based serological diagnostic for C. trachomatis related infertility in women. A bioinformatics analysis was conducted examining several immunodominant proteins from C. trachomatis to identify predicted immunoglobulin epitopes unique to C. trachomatis. A peptide array of these epitopes was screened against participant sera. The participants (all female) were categorized into the following cohorts based on their infection and gynecological history; acute (single treated infection with C. trachomatis), multiple (more than one C. trachomatis infection, all treated), sequelae (PID or tubal infertility with a history of C. trachomatis infection), and infertile (no history of C. trachomatis infection and no detected tubal damage). The bioinformatics strategy identified several promising epitopes. Participants who reacted positively in the peptide 11 ELISA were found to have an increased likelihood of being in the sequelae cohort compared to the infertile cohort with an odds ratio of 16.3 (95% c.i. 1.65-160), with 95% specificity and 46% sensitivity (0.19-0.74). The peptide 11 ELISA has the potential to be further developed as a screening tool for use during the early IVF work up and provides proof of concept that there may be further peptide antigens which could be identified using bioinformatics and screening approaches. © 2013 The Authors

A preliminary audit of medical and aid provision in English Rugby union clubs:compliance with Regulation 9

BackgroundGoverning bodies are largely responsible for the monitoring and management of risks associated with a safe playing environment, yet adherence to regulations is currently unknown. The aim of this study was to investigate and evaluate the current status of medical personnel, facilities, and equipment in Rugby Union clubs at regional level in England.MethodsA nationwide cross-sectional survey of 242 registered clubs was undertaken, where clubs were surveyed online on their current medical personnel, facilities, and equipment provision, according to regulation 9 of the Rugby Football Union (RFU).ResultsOverall, 91 (45. 04%) surveys were returned from the successfully contacted recipients. Of the completed responses, only 23.61% (n = 17) were found to be compliant with regulations. Furthermore, 30.56% (n = 22) of clubs were unsure if their medical personnel had required qualifications; thus, compliance could not be determined. There was a significant correlation (p = −0.029, r = 0.295) between club level and numbers of practitioners. There was no significant correlation indicated between the number of practitioners/number of teams and number of practitioners/number of players. There were significant correlations found between club level and equipment score (p = 0.003, r = −0.410), club level and automated external defibrillator (AED) access (p = 0.002, r = −0.352) and practitioner level and AED access (p = 0.0001, r = 0.404). Follow-up, thematic analysis highlighted widespread club concern around funding/cost, awareness, availability of practitioners and AED training.ConclusionThe proportion of clubs not adhering overall compliance with Regulation 9 of the RFU is concerning for player welfare, and an overhaul, nationally, is required

Rosetta-Alice Observations of Exospheric Hydrogen and Oxygen on Mars

The European Space Agency's Rosetta spacecraft, en route to a 2014 encounter with comet 67P/Churyumov-Gerasimenko, made a gravity assist swing-by of Mars on 25 February 2007, closest approach being at 01:54UT. The Alice instrument on board Rosetta, a lightweight far-ultraviolet imaging spectrograph optimized for in situ cometary spectroscopy in the 750-2000 A spectral band, was used to study the daytime Mars upper atmosphere including emissions from exospheric hydrogen and oxygen. Offset pointing, obtained five hours before closest approach, enabled us to detect and map the HI Lyman-alpha and Lyman-beta emissions from exospheric hydrogen out beyond 30,000 km from the planet's center. These data are fit with a Chamberlain exospheric model from which we derive the hydrogen density at the 200 km exobase and the H escape flux. The results are comparable to those found from the the Ultraviolet Spectrometer experiment on the Mariner 6 and 7 fly-bys of Mars in 1969. Atomic oxygen emission at 1304 A is detected at altitudes of 400 to 1000 km above the limb during limb scans shortly after closest approach. However, the derived oxygen scale height is not consistent with recent models of oxygen escape based on the production of suprathermal oxygen atoms by the dissociative recombination of O2+.Comment: 17 pages, 8 figures, accepted for publication in Icaru

2015 ACVIM Small Animal Consensus Statement on Seizure Management in Dogs

This report represents a scientific and working clinical consensus statement on seizure management in dogs based on current literature and clinical expertise. The goal was to establish guidelines for a predetermined, concise, and logical sequential approach to chronic seizure management starting with seizure identification and diagnosis (not included in this report), reviewing decision‐making, treatment strategies, focusing on issues related to chronic antiepileptic drug treatment response and monitoring, and guidelines to enhance patient response and quality of life. Ultimately, we hope to provide a foundation for ongoing and future clinical epilepsy research in veterinary medicine

Educational paper: Primary immunodeficiencies in children: a diagnostic challenge

Primary immunodeficiencies (PIDs) are characterized by an increased susceptibility to infections due to defects in one ore more components of the immune system. Although most PIDs are relatively rare, they are more frequent than generally acknowledged. Early diagnosis and treatment of PIDs save lives, prevent morbidity, and improve quality of life. This early diagnosis is the task of the pediatrician who encounters the child for the first time: he/she should suspect potential PID in time and perform the appropriate diagnostic tests. In this educational paper, the first in a series of five, we will describe the most common clinical presentations of PIDs and offer guidelines for the diagnostic process, as well as a brief overview of therapeutic possibilities and prognosis

Emerging Infectious Disease leads to Rapid Population Decline of Common British Birds

Emerging infectious diseases are increasingly cited as threats to wildlife, livestock and humans alike. They can threaten geographically isolated or critically endangered wildlife populations; however, relatively few studies have clearly demonstrated the extent to which emerging diseases can impact populations of common wildlife species. Here, we report the impact of an emerging protozoal disease on British populations of greenfinch Carduelis chloris and chaffinch Fringilla coelebs, two of the most common birds in Britain. Morphological and molecular analyses showed this to be due to Trichomonas gallinae. Trichomonosis emerged as a novel fatal disease of finches in Britain in 2005 and rapidly became epidemic within greenfinch, and to a lesser extent chaffinch, populations in 2006. By 2007, breeding populations of greenfinches and chaffinches in the geographic region of highest disease incidence had decreased by 35% and 21% respectively, representing mortality in excess of half a million birds. In contrast, declines were less pronounced or absent in these species in regions where the disease was found in intermediate or low incidence. Also, populations of dunnock Prunella modularis, which similarly feeds in gardens, but in which T. gallinae was rarely recorded, did not decline. This is the first trichomonosis epidemic reported in the scientific literature to negatively impact populations of free-ranging non-columbiform species, and such levels of mortality and decline due to an emerging infectious disease are unprecedented in British wild bird populations. This disease emergence event demonstrates the potential for a protozoan parasite to jump avian host taxonomic groups with dramatic effect over a short time period

Crucial Role of the CB3-Region of Collagen IV in PARF-Induced Acute Rheumatic Fever

Acute rheumatic fever (ARF) and rheumatic heart disease are serious autoimmune sequelae to infections with Streptococcus pyogenes. Streptococcal M-proteins have been implicated in ARF pathogenesis. Their interaction with collagen type IV (CIV) is a triggering step that induces generation of collagen-specific auto-antibodies. Electron microscopy of the protein complex between M-protein type 3 (M3-protein) and CIV identified two prominent binding sites of which one is situated in the CB3-region of CIV. In a radioactive binding assay, M3-protein expressing S. pyogenes and S. gordonii bound the CB3-fragment. Detailed analysis of the interactions by surface plasmon resonance measurements and site directed mutagenesis revealed high affinity interactions with dissociation constants in the nanomolar range that depend on the recently described collagen binding motif of streptococcal M-proteins. Because of its role in the induction of disease-related collagen autoimmunity the motif is referred to as “peptide associated with rheumatic fever” (PARF). Both, sera of mice immunized with M3-protein as well as sera from patients with ARF contained anti-CB3 auto-antibodies, indicating their contribution to ARF pathogenesis. The identification of the CB3-region as a binding partner for PARF directs the further approaches to understand the unusual autoimmune pathogenesis of PARF-dependent ARF and forms a molecular basis for a diagnostic test that detects rheumatogenic streptococci

Methylation of hMLH1 promoter correlates with the gene silencing with a region-specific manner in colorectal cancer

Microsatellite instability is present in over 80% of the hereditary non-polyposis colorectal carcinoma and about 15–20% of the sporadic cancer. Microsatellite instability is caused by the inactivation of the mismatch repair genes, such as primarily hMLH1, hMSH2. To study the mechanisms of the inactivation of mismatch repair genes in colorectal cancers, especially the region-specific methylation of hMLH1 promoter and its correlation with gene expression, we analysed microsatellite instability, expression and methylation of hMLH1 and loss of heterozygosity at hMLH1 locus in these samples. Microsatellite instability was present in 17 of 71 primary tumours of colorectal cancer, including 14 of 39 (36%) mucinous cancer and three of 32 (9%) non-mucinous cancer. Loss of hMLH1 and hMSH2 expression was detected in nine and three of 16 microsatellite instability tumours respectively. Methylation at CpG sites in a proximal region of hMLH1 promoter was detected in seven of nine tumours that showed no hMLH1 expression, while no methylation was present in normal mucosa and tumours which express hMLH1. However, methylation in the distal region was observed in all tissues including normal mucosa and hMLH1 expressing tumours. This observation indicates that methylation of hMLH1 promoter plays an important role in microsatellite instability with a region-specific manner in colorectal cancer. Loss of heterozygosity at hMLH1 locus was present in four of 17 cell lines and 16 of 54 tumours with normal hMLH1 status, while loss of heterozygosity was absent in all nine cell lines and nine tumours with abnormal hMLH1 status (mutation or loss of expression), showing loss of heterozygosity is not frequently involved in the inactivation of hMLH1 gene in sporadic colorectal cancer

Adaptation to Delayed Force Perturbations in Reaching Movements

Adaptation to deterministic force perturbations during reaching movements was extensively studied in the last few decades. Here, we use this methodology to explore the ability of the brain to adapt to a delayed velocity-dependent force field. Two groups of subjects preformed a standard reaching experiment under a velocity dependent force field. The force was either immediately proportional to the current velocity (Control) or lagged it by 50 ms (Test). The results demonstrate clear adaptation to the delayed force perturbations. Deviations from a straight line during catch trials were shifted in time compared to post-adaptation to a non-delayed velocity dependent field (Control), indicating expectation to the delayed force field. Adaptation to force fields is considered to be a process in which the motor system predicts the forces to be expected based on the state that a limb will assume in response to motor commands. This study demonstrates for the first time that the temporal window of this prediction needs not to be fixed. This is relevant to the ability of the adaptive mechanisms to compensate for variability in the transmission of information across the sensory-motor system