Cobalt accumulation in horses following repeated administration of cobalt chloride.

OBJECTIVE: To monitor cobalt concentrations in urine, red blood cells and plasma after chronic parenteral administration of cobalt chloride evaluate these results against the current International Federation of Horseracing Authorities thresholds for detecting cobalt misuse. DESIGN: Eight mares were randomly assigned to four treatment groups, with two mares in each group: Group 1 - control group, Group 2 - 25 milligrams cobalt intravenously as CoCl2 weekly, Group 3 - 50 milligrams cobalt intravenously as CoCl2 weekly, and Group 4 - 25 milligrams cobalt intravenously mid-week and at the end of the week. Urine and blood samples were collected before each weekly administration so that trough levels were assessed. In the group receiving two doses per week, urine and blood were collected prior to the dose given at the end of each week. Samples were initially collected at time zero then weekly for 10 weeks. Three further collections of urine and blood were made at days 81, 106 and 127. METHODS: Urine creatinine measurements to assess horse hydration status were performed by the Jaffe reaction method. Cobalt determinations in plasma, blood and urine were by inductively coupled plasma-mass spectrometry. Haematocrit concentrations, used to calculate red cell cobalt levels, were performed using a microhematocrit centrifuge. Statistical analyses were conducted in Genstat (v17, VSNi). RESULTS: Marked cobalt accumulation was evident with increasing cobalt concentrations for all sample matrices in specimens collected immediately prior to cobalt administration. Correlation between the sample matrices improved when urine cobalt concentration was adjusted for creatinine level. Red cell cobalt levels remained elevated for at least 12 weeks after cessation of administration, consistent with the lifespan of the red cell. There was no significant change in haematocrit concentrations for the duration of the study. CONCLUSION: The current urine cobalt threshold was only effective at detecting acute cobalt exposure while the plasma cobalt threshold was able to consistently identify chronic high-level cobalt exposure and potential cobalt misuse. The threshold values legislated for urine cobalt do not correlate with those set for plasma. The acute nature of urinary cobalt excretion provides a relatively small window through which cobalt administration is detected. Plasma and red cell cobalt concentrations can provide a clearer picture of potential cobalt misuse.

Prospecting for an HIV vaccine.

Human immunodeficiency virus (HIV) sets several challenges for the development of a preventative HIV vaccine. Predictable, protective natural immunity against HIV does not occur and so unlike most other diseases for which vaccines exist, there are few guideposts from natural infection. Nonetheless, six vaccine efficacy trials have occurred. One in particular, the Thai trial called RV144, showed partial protective efficacy and potential ways ahead to a better vaccine approach. This coupled with other lessons from studies of acute infections as well as an increasingly complex knowledge of HIV-related vaccine immunology bring hope that a vaccine solution might be reached for this pervasive and deadly pandemic.

Modulation of the Surface-Layer Protein of Clostridium difficile through Cwp84 Inhibition.

Cysteine protease Cwp84 is responsible for surface-layer processing in Clostridium difficile and was also shown to cleave several human extracellular matrix components in vitro. To enable the facile identification and characterization of Cwp84 inhibitors, we developed a fluorogenic 10-mer peptide based on the enzyme's natural substrate SlpA that is amenable for use in FRET-based high-throughput screening. The design of substrate-mimetic inhibitors led to epoxysuccinate 8c, which displayed an inactivation efficiency (kinact/KI) of (4.7 ± 0.3) × 10(4) M(-1) min(-1). Further evaluation of 8c demonstrated its ability to inhibit fibronectin cleavage and, more importantly, subvert surface-layer biogenesis in C. difficile.

Practical Aspects of Multiscale Classical and Quantum Simulations of Enzyme Reactions.

This chapter aims to present some basic multiscale approaches available for enzyme simulations, and to point out practical details and pitfalls that are not often discussed in the literature, but can greatly influence the outcome of any in silico enzyme study. We cover principle methodological steps of multiscale studies of general enzyme reactions. This includes choice of starting structures, boundary conditions, potential energy surfaces, reaction coordinates, simulation methods, as well as the choice of method for the treatment of nuclear quantum effects. Together, these and additional steps are crucial for the success of enzyme-modeling projects and should be considered prior to embarking on multiscale modeling.

Are you PEPped and PrEPped for travel? Risk mitigation of HIV infection for travelers.

The HIV pandemic persists globally and travelers are at risk for infection by the Human Immunodeficiency Virus (HIV). While HIV-focused guidelines delineate risk stratification and mitigation strategies for people in their home communities, travel issues are not addressed. In this review, direct and indirect evidence on HIV risk among travelers is explored. The burgeoning practice of employing pre-exposure prophylaxis (PrEP) with anti-retroviral therapy in the non-travel setting is introduced, as well as the more established use of post-exposure prophylaxis (PEP). Challenges in applying these lessons to travelers are discussed, and a new guidelines process is scoped and recommended.

Recent trends in breast, cervical, and colorectal cancer screening test utilization in Canada, using self-reported data from 2008 and 2012.

In Canada, self-reported data from the Canadian Community Health Survey 2008 and 2012 provide an opportunity to examine overall utilization of breast, cervical, and colorectal cancer screening tests for both programmatic and opportunistic screening. Among women 50-74 years of age, utilization of screening mammography was stable (62.0% in 2008 and 63.0% in 2012). Pap test utilization for women 25-69 years of age remained high and stable across Canada in 2008 and 2012 (78.9% in 2012). The percentage of individuals 50-74 years of age who reporting having at least 1 fecal test within the preceding 2 years increased in 2012 (to 23.0% from 16.9% in 2008), but remains low. Stable rates of screening mammography utilization (about 30%) were reported in 2008 and 2012 among women 40-49 years of age, a group for which population-based screening is not recommended. Although declining over time, cervical cancer screening rates were high for women less than 25 years of age (for whom screening is not recommended). Interestingly, an increased percentage of women 70-74 years of age reported having a Pap test. In 2012, a smaller percentage of women 50-69 years of age reported having no screening test (5.9% vs. 8.5% in 2008), and more women reported having the three types of cancer screening tests (19.0% vs. 13.2%). Efforts to encourage use of screening within the recommended average-risk age groups are needed, and education for stakeholders about the possible harms of screening outside those age groups has to continue.

Healthcare workers' attitude towards influenza vaccination after the 2009 pandemic.

BACKGROUND: Previous studies have demonstrated the variability of healthcare workers' (HCWs) willingness to consider seasonal influenza vaccination, possibly to the detriment of their patients. AIMS: To ascertain HCW uptake of H1N1 and seasonal influenza vaccination and the reasons why one or both might have been declined following the pandemic of 2009. METHODS: An online, anonymous survey of HCWs across five, acute National Health Service trusts was undertaken in 2010. RESULTS: A total of 765 responses were obtained, of which the two main groups of participants were doctors of all grades (42%) and qualified nurses (40%). The willingness to be vaccinated increased with age. Senior doctors were the occupational group most likely to have had both vaccinations, but where they did decline they mainly did so because they perceived influenza to be a minor illness. Females were more likely to decline vaccination due to a fear of side effects, whereas males, particularly younger ones, viewed influenza as a minor illness. Junior doctors cited lack of availability of immunization sessions as one of the main reasons why they may not have had vaccination. CONCLUSIONS: Future influenza vaccination campaigns should consider using different approaches depending on the gender and occupational mix of the target population, rather than adopting a 'one-size' fits all approach.

Injury rate and injury pattern among elite World Cup snowboarders: a 6-year cohort study.

BACKGROUND: There is limited knowledge on the injury rate and injury pattern in the different disciplines among elite snowboarders. OBJECTIVE: The aim of this study was to describe and compare the injury rate and injury pattern among the different International Ski Federation (Fédération Internationale de Ski, FIS) World Cup (WC) snowboard disciplines. METHODS: We conducted retrospective interviews with FIS WC snowboard athletes at the end of each season in the period 2007-2012, to register all acute injuries sustained during training or competition during the competitive season requiring attention by medical personnel. To calculate the exposure, we obtained information from result lists from the FIS competition database for all WC competitions for each of the interviewed athletes. RESULTS: We registered a total of 574 injuries among 1432 athletes, accounting for an overall injury rate of 40.1 injuries/100 athlete/season. A total of 171 injuries occurred during the FIS WC competitions, corresponding to 6.4 injuries/1000 runs. During competition, injury risk was highest in snowboard cross with 11.9/1000 runs, followed by 6.3 in halfpipe, 3.6 in big air and 2.8 in parallel giant slalom/parallel slalom (PGS/PSL). Snowboard cross also had the highest risk of severe injuries (>28 days absence). No differences in injury risk were detected between male and female snowboarders. The most commonly injured body part was the knee (17.8%), followed by the shoulder/clavicle (13.4%) and head/face (13.2%). The risk of knee injury (the most common injury type) and head injury was significantly higher in snowboard cross and halfpipe compared to PGS/PSL. CONCLUSIONS: The risk of injuries was higher in snowboard cross than in halfpipe, big air and PGS/PSL. The most commonly injured body part was the knee. Prevention of snowboard injuries among elite snowboarders should focus on knee injuries, severe injuries and snowboard cross athletes.

Colorectal cancer screening in Canada: results from the first round of screening for five provincial programs.

BACKGROUND: Early implementation of programmatic colorectal cancer (crc) screening for average-risk individuals 50-74 years of age in Canada has used fecal occult blood tests [fts (guaiac or immunochemical)] and colonoscopy for follow-up of abnormal fts. This paper presents results of an evaluation of this crc screening. METHODS: Five Canadian provincial programs provided aggregated data for individuals with a first-round ft processed between January 1, 2009, and December 31, 2011. RESULTS: The 104,750 people who successfully completed a first round of screening represented 16.1% of those who had access to the programs between January 1, 2009, and December 31, 2011 (mean age: 61.2 years; men: 61.4 years; women: 61.1 years). Of those participants, 4661 had an abnormal ft (4.4%). Uptake of colonoscopy within 180 days after an abnormal ft was 80.5%, ranging from 67.8% to 89.5% by program. The positive predictive value (ppv) for adenoma was 35.9% for guaiac ft and 50.6% for immunochemical ft. Adenoma and crc detection rates were, respectively, 16.9 and 1.8 per 1000 screened. Of invasive crcs detected, 64.6% were stage i or ii. CONCLUSIONS: Considering the variation in characteristics and stage of implementation of each provincial program, the collaboration of the provinces leading to this report on the early performance of crc screening in Canada is a major milestone. Targets are met or nearly met for significant indicators such as ppv for adenoma and cancer detection rate. Participation is expected to increase as programs are fully implemented in the provinces. Additional effort may be needed to improve timely access to follow-up colonoscopy.

A review of screening mammography participation and utilization in Canada.

INTRODUCTION: Participation rate is an important indicator for a screening program's effectiveness; however, the current approach to measuring participation rate in Canada is not comparable with other countries. The objective of this study is to review the measurement of screening mammography participation in Canada, make international comparisons, and propose alternative methods. METHODS: Canadian breast cancer screening program data for women aged 50 to 69 years screened between 2004 and 2006 were extracted from the Canadian Breast Cancer Screening Database (CBCSD). The fee-for-services (FSS) mammography data (opportunistic screening mammography) were obtained from the provincial ministries of health. Both screening mammography program participation and utilization were examined over 24 and 30 months. RESULTS: Canada's screening participation rate increases from 39.4% for a 24-month cut-off to 43.6% for a 30-month cut-off. The 24-month mammography utilization rate is 63.1% in Canada, and the 30-month utilization rate is 70.4%. CONCLUSION: Due to the differences in health service delivery among Canadian provinces, both programmatic participation and overall utilization of mammography at 24 months and 30 months should be monitored.

Pan-Canadian initiatives in colorectal cancer screening: adopting knowledge translation tools to accelerate uptake and impact.

BACKGROUND: Despite the positive conclusions of several randomized controlled trials and the publication of national recommendations on colorectal cancer (crc) screening, uptake remained low. The inauguration of the National Colorectal Cancer Screening Network in 2007, the same year that the first screening program was announced in Canada, provided an opportunity for integrated knowledge translation to accelerate the processes of program implementation and screening uptake. AIM: Two primary aims were identified. The first focused on means to monitor the effects of various implementation plans in delivering high-quality population-based crc screening. The second focused on identifying and addressing knowledge gaps that may impair screening participation. METHOD: The methods used are described in the context of the knowledge-to-action cycle and demonstrate that the initiative itself dictates the point in the cycle at which to start. RESULTS: The identified need to monitor various implementation plans resulted in the shared development of a quality determinants document. All programs committed to designing data collection so that core components could be measured and compared; 6 operating programs have conducted the first data collection, which will allow for monitoring and for new knowledge creation as the process develops further. The knowledge gap identification project started with new knowledge creation, which identified a higher-than-expected willingness of Canadians to discuss crc screening with physicians, but a low level of understanding of screening as a wellness-related behaviour. Knowledge translation interventions have been developed with the stakeholders to address those gaps, and ongoing surveys to be carried out later in 2011 will help to gauge progress in the understanding and acceptance of crc screening by the population. CONCLUSIONS: A national network that engaged all programs, policymakers, experts, and lay representatives successfully used knowledge translation principles to enhance the trajectory of crc screening in Canada.

Behaviour of equine influenza virus in a naïve population: a practitioner's perspective.

We describe the behaviour of equine influenza (EI) virus infection in a naïve population as observed by equine veterinary practitioners. The clinical signs displayed by infected horses and the highly contagious nature of the disease are discussed, as well as the treatment and management of infected horses.

Spatial association and clinical development of equine influenza in horses yarded overnight at an equestrian event at Maitland prior to propagating the 2007 epidemic in Australia.

The interaction and stabling of horses at equine events may have a substantial impact on the spread of a zoonotic disease. This study aimed to investigate the spread of equine influenza (EI) at an equestrian event at the start of the Australian outbreak. Around one-third of the competing horses were stabled overnight at the event and, of these, 70% developed symptoms of EI within 7 days. The index case was never positively identified, but stabling position and disease onset provided clues to its potential identity.

Hygiene practices to prevent the spread of equine influenza by humans.

This paper describes a protocol for hygiene practices that was devised by a practice in which all veterinarians were involved on a daily basis in visiting infected premises, including sampling, treatment of clinical cases and general veterinary work. This protocol was strictly followed when attending an infected or at risk property.

Acute lameness associated with osseous metastasis of a peri-renal carcinoma in a horse.

We present a case of aggressive metastatic carcinoma in a horse that was initially presented for shoulder lameness. Although radiography and scintigraphy were useful for localising a lesion in the proximal humerus, subsequent development of non-specific signs of systemic disease prompted further evaluation. Haematology and blood biochemistry, urinalysis and ultrasonography were all instrumental in identifying renal involvement. A diagnosis of a peri-renal mass causing secondary renal failure prompted euthanasia of the horse because of the poor prognosis. Antemortem findings were supported by necropsy, with secondary lesions also identified in the spleen, liver, 8th left rib and proximal humerus. Histological examination yielded a diagnosis of undifferentiated metastatic carcinoma.

Variations in expression of carbon isotope fractionation of chlorinated ethenes during biologically enhanced PCE dissolution close to a source zone.

The stable carbon isotope values of tetrachloroethene (PCE) and its degradation products were monitored during studies of biologically enhanced dissolution of PCE dense nonaqueous phase liquid (DNAPL) to determine the effect of PCE dissolution on observed isotope values. The degradation of PCE was monitored in a 2-dimensional model aquifer and in a pilot test cell (PTC) at Dover Air Force Base, both with emplaced PCE DNAPL sources. Within the plume down gradient from the source, the isotopic fractionation of dissolved PCE and its degradation products were consistent with those observed in biodegradation laboratory studies. However, close to the source zone significant shifts in the isotope values of dissolved PCE were not observed in either the model aquifer or PTC due to the constant input of newly dissolved, non fractionated PCE, and the small isotopic fractionation associated with PCE reductive dechlorination by the mixed microbial culture used. Therefore the identification of reductive dechlorination in the presence of PCE DNAPL was based upon the appearance of daughter products and the isotope values of those daughter products. An isotope model was developed to simulate isotope values of PCE during the dissolution and degradation of PCE adjacent to a DNAPL source zone. With the exception of very high degradation rate constants (>1/day) stable carbon isotope values of PCE estimated by the model remained within error of the isotope value of the PCE DNAPL, consistent with measured isotope values in the model aquifer and in the PTC.