THE EFFECT OF CMV INFECTION ON PROGRESSION OF HUMAN-IMMUNODEFICIENCY-VIRUS DISEASE IN A COHORT OF HEMOPHILIC MEN FOLLOWED FOR UP TO 13 YEARS FROM SEROCONVERSION

The effect of prior infection with cytomegalovirus (CMV) on progression of HIV disease in a cohort of 111 men with haemophilia was studied after 13 years followup. The relative hazards associated with CMV positivity on progression to AIDS, death and a CD4 count of 0.05 x 10(9)/l were 2.28, 2.42 and 2.34, respectively. CMV seropositive patients were significantly older than the seronegative and this was controlled for by using a Cox proportional hazards model. The relative hazards for the three endpoints decreased to 1.89, 1.82 and 1.93 respectively and were marginally non-significant (P = 0.05, 0.08 and 0.08 for the three endpoints respectively). We conclude that this cohort continues to show evidence of a 'co-factor' effect associated with prior infection with CMV which is confounded by age but not completely explained by age differences. The potential biological significance of these results is discussed in the context of recent controlled clinical trials which show a survival benefit from long-term high-dose acyclovir, a drug with activity in vivo against CMV and other herpesviruses

Combined Inflammatory and Metabolic Defects Reflected by Reduced Serum Protein Levels in Patients with Buruli Ulcer Disease

Buruli ulcer is a skin disease caused by Mycobacterium ulcerans that is spreading in tropical countries, with major public health and economic implications in West Africa. Multi-analyte profiling of serum proteins in patients and endemic controls revealed that Buruli ulcer disease down-regulates the circulating levels of a large array of inflammatory mediators, without impacting on the leukocyte composition of peripheral blood. Notably, several proteins contributing to acute phase reaction, lipid metabolism, coagulation and tissue remodelling were also impacted. Their down-regulation was selective and persisted after the elimination of bacteria with antibiotic therapy. It involved proteins with various functions and origins, suggesting that M. ulcerans infection causes global and chronic defects in the host’s protein metabolism. Accordingly, patients had reduced levels of total serum proteins and blood urea, in the absence of signs of malnutrition, or functional failure of liver or kidney. Interestingly, slow healers had deeper metabolic and coagulation defects at the start of antibiotic therapy. In addition to providing novel insight into Buruli ulcer pathogenesis, our study therefore identifies a unique proteomic signature for this disease

Mycobacterium ulcerans DNA Not Detected in Faecal Samples from Buruli Ulcer Patients: Results of a Pilot Study

It has recently been shown that in a Buruli ulcer (BU) endemic region of southeastern Australia, significant numbers of possums (native tree-dwelling marsupials) have clinical BU disease. Furthermore, based on quantitative PCR (qPCR) analysis, animals with BU lesions (and some without) shed M. ulcerans DNA in their faeces, indicative of bacterial loads of up to 108 organisms/gram. These findings led us to propose that humans might also harbour M. ulcerans in their gastrointestinal tract and shed the bacterium in their faeces. We conducted a pilot study and collected faecal swabs from 26 patients with confirmed BU and 31 healthy household controls. Faecal samples were also collected from 10 healthy controls from non-endemic regions in Ghana. All 67 specimens were negative when tested by IS2404 PCR. The detection sensitivity of this method was ≥104 bacteria per gram (wet-weight) of human faecal material. We conclude that the human gastrointestinal tract is unlikely to be a significant reservoir of M. ulcerans

UK survey of occupational therapist’s and physiotherapist’s experiences and attitudes towards hip replacement precautions and equipment

Background: Total hip replacement (THR) is one of the most common orthopaedic procedures in the United Kingdom (UK). Historically, people following THR have been provided with hip precautions and equipment such as: raised toilet seats and furniture rises, in order to reduce the risks of dislocation post-operation. The purpose of this study was to determine current practices in the provision of these interventions in the UK for people following primary THR. Methods: A 27-question, self-administered online survey was developed and distributed to UK physiotherapists and occupational therapists involved in the management of people following primary THR (target respondents). The survey included questions regarding the current practices in the provision of equipment and hip precautions for THR patients, and physiotherapist’s and occupational therapist’s attitudes towards these practices. The survey was disseminated through print and web-based/social media channels. Results: 170 health professionals (87 physiotherapists and 83 occupational therapists), responded to the survey. Commonly prescribed equipment in respondent’s health trusts were raised toilet seats (95%), toilet frames and rails (88%), furniture raises (79%), helping hands/grabbers (77%), perching stools (75%) and long-handled shoe horns (75%). Hip precautions were routinely prescribed by 97% of respondents. Hip precautions were most frequently taught in a pre-operative group (52% of respondents). Similarly equipment was most frequently provided pre-operatively (61% respondents), and most commonly by occupational therapists (74% respondents). There was variability in the advice provided on the duration of hip precautions and equipment from up to six weeks post-operatively to life-time usage. Conclusions: Current practice on hip precautions and provision of equipment is not full representative of clinician’s perceptions of best care after THR. Future research is warranted to determine whether and to whom hip precautions and equipment should be prescribed post-THR as opposed to the current ‘blanket’ provision of equipment and movement restriction provided in UK practice

Mycolactone Diffuses into the Peripheral Blood of Buruli Ulcer Patients - Implications for Diagnosis and Disease Monitoring.

BACKGROUND: Mycobacterium ulcerans, the causative agent of Buruli ulcer (BU), is unique among human pathogens in its capacity to produce a polyketide-derived macrolide called mycolactone, making this molecule an attractive candidate target for diagnosis and disease monitoring. Whether mycolactone diffuses from ulcerated lesions in clinically accessible samples and is modulated by antibiotic therapy remained to be established. METHODOLOGY/PRINCIPAL FINDING: Peripheral blood and ulcer exudates were sampled from patients at various stages of antibiotic therapy in Ghana and Ivory Coast. Total lipids were extracted from serum, white cell pellets and ulcer exudates with organic solvents. The presence of mycolactone in these extracts was then analyzed by a recently published, field-friendly method using thin layer chromatography and fluorescence detection. This approach did not allow us to detect mycolactone accurately, because of a high background due to co-extracted human lipids. We thus used a previously established approach based on high performance liquid chromatography coupled to mass spectrometry. By this means, we could identify structurally intact mycolactone in ulcer exudates and serum of patients, and evaluate the impact of antibiotic treatment on the concentration of mycolactone. CONCLUSIONS/SIGNIFICANCE: Our study provides the proof of concept that assays based on mycolactone detection in serum and ulcer exudates can form the basis of BU diagnostic tests. However, the identification of mycolactone required a technology that is not compatible with field conditions and point-of-care assays for mycolactone detection remain to be worked out. Notably, we found mycolactone in ulcer exudates harvested at the end of antibiotic therapy, suggesting that the toxin is eliminated by BU patients at a slow rate. Our results also indicated that mycolactone titres in the serum may reflect a positive response to antibiotics, a possibility that it will be interesting to examine further through longitudinal studies

The First Shared Online Curriculum Resources for Veterinary Undergraduate Learning and Teaching in Animal Welfare and Ethics in Australia and New Zealand

The need for undergraduate teaching of Animal Welfare and Ethics (AWE) in Australian and New Zealand veterinary courses reflects increasing community concerns and expectations about AWE; global pressures regarding food security and sustainability; the demands of veterinary accreditation; and fears that, unless students encounter AWE as part of their formal education, as veterinarians they will be relatively unaware of the discipline of animal welfare science. To address this need we are developing online resources to ensure Australian and New Zealand veterinary graduates have the knowledge, and the research, communication and critical reasoning skills, to fulfill the AWE role demanded of them by contemporary society. To prioritize development of these resources we assembled leaders in the field of AWE education from the eight veterinary schools in Australia and New Zealand and used modified deliberative polling. This paper describes the role of the poll in developing the first shared online curriculum resource for veterinary undergraduate learning and teaching in AWE in Australia and New Zealand. The learning and teaching strategies that ranked highest in the exercise were: scenario-based learning; a quality of animal life assessment tool; the so-called ‘Human Continuum’ discussion platform; and a negotiated curriculum. Keywords: animal ethics; animal welfare; online curriculum resources; learning and teaching; scenarios; quality of life assessmentALT gran

Questionnaire study to gain an insight into the manufacturing and fitting process of artificial eyes in children: an ocularist perspective

Purpose To gain an insight into the manufacturing and fitting of artificial eyes in children and potential improvements to the process. Method An online qualitative survey was distributed to 39 ocularists/prosthetists in Europe and Canada. Participants were recruited through purposive sampling, specifically maximum variation sampling from the researcher’s contacts and an online search. Results The findings highlighted the current impression technique as being the most difficult yet most important part of the current process for both the ocularist and child patient. Negatively affecting obtaining a good impression, the child patients distress can be reduced by their parents by providing encouragement, reassurance, practicing the insertion and removal of the artificial eye and being matter of fact. Whilst improvements to the current process provided mixed views, the incorporation of current technology was perceived as not being able to meet the requirements to produce aesthetically pleasing artificial eyes. Conclusion The current artificial eye process can be seen as an interaction with its success being dependent on the child patient’s acceptance and adjustment which is dependent on the factors associated to the process. Investigation into the needs of the patient and whether technology can improve the process are the next steps in its advancement

Hepatic DNA damage in harbour porpoises (Phocoena phocoena) stranded along the English and Welsh coastlines

One level at which persistent organic pollutants (POPs) and polycyclic aromatic hydrocarbons PAHs) can exert damage is by causing DNA strand-breaks or nucleotide base modifications, which, if unrepaired, can lead to embryonic mutations, abnormal development and cancer. In marine ecosystems, genotoxicity is expected to be particularly strong in long-lived apex predators due to pollutant bioaccumulation. We conducted 32 P-postlabeling analyses optimized for the detection and quantification of aromatic/hydrophobic DNA adducts in the livers of 40 sexually-mature North Atlantic harbour porpoises (Phocoena phocoena) stranded along the English and Welsh coastlines. We examined hepatic tissue to search for inflammatory and preneoplastic lesions and examine their association with adduct levels. Adducts were found in all porpoises (mean: 17.56 ± 11.95 per 108 nucleotides), and were higher than levels reported for marine vertebrates from polluted sites. The pollutants causing the induced DNA adducts could not be further characterized. Hepatic DNA damage did not correlate with levels of blubber POP concentrations (including total polychlorinated biphenyl [PCBs], dichlorodiphenyltrichloroethane [DDT] and dieldrin); PAH concentrations were not available for the present study. However, DNA damage predicted occurrence of inflammatory and preneoplastic lesions. Further, our data showed a reduction in hepatic DNA adduct levels with age in the 40 animals examined while POP concentrations, particularly PCBs, increased with age. Using a different dataset of 145 mature male harbour porpoises confirmed that higher contaminant levels (total PCBs, DDT and dieldrin) are found in older animals. The reduction in hepatic DNA adduct levels in older animals was in accordance with other studies which show that suppression of hepatic CYP1A enzyme activity at high PCB concentrations might impact on CYP1A-mediated DNA adduct formation of PAHs which are ubiquitous environmental pollutants and readily metabolized by CYP1A to species binding to DNA. In summary, our study shows that pollutant-induced DNA damage is prevalent in harbour porpoises from UK waters and may lead to detectable sub-lethal hepatic damage

Air–sea exchange of acetone, acetaldehyde, DMS and isoprene at a UK coastal site

Volatile organic compounds (VOCs) are ubiquitous in the atmosphere and are important for atmospheric chemistry. Large uncertainties remain in the role of the ocean in the atmospheric VOC budget because of poorly constrained marine sources and sinks. There are very few direct measurements of air–sea VOC fluxes near the coast, where natural marine emissions could influence coastal air quality (i.e. ozone, aerosols) and terrestrial gaseous emissions could be taken up by the coastal seas. To address this, we present air–sea flux measurements of acetone, acetaldehyde and dimethylsulfide (DMS) at the coastal Penlee Point Atmospheric Observatory (PPAO) in the south-west UK during the spring (April–May 2018). Fluxes of these gases were measured simultaneously by eddy covariance (EC) using a proton-transfer-reaction quadrupole mass spectrometer. Comparisons are made between two wind sectors representative of different air–water exchange regimes: the open-water sector facing the North Atlantic Ocean and the terrestrially influenced Plymouth Sound fed by two estuaries. Mean EC (± 1 standard error) fluxes of acetone, acetaldehyde and DMS from the open-water wind sector were −8.0 ± 0.8, −1.6 ± 1.4 and 4.7 ± 0.6 µmol m−2 d−1 respectively (“−” sign indicates net air-to-sea deposition). These measurements are generally comparable (same order of magnitude) to previous measurements in the eastern North Atlantic Ocean at the same latitude. In comparison, the Plymouth Sound wind sector showed respective fluxes of −12.9 ± 1.4, −4.5 ± 1.7 and 1.8 ± 0.8 µmol m−2 d −1. The greater deposition fluxes of acetone and acetaldehyde within the Plymouth Sound were likely to a large degree driven by higher atmospheric concentrations from the terrestrial wind sector. The reduced DMS emission from the Plymouth Sound was caused by a combination of lower wind speed and likely lower dissolved concentrations as a result of the estuarine influence (i.e. dilution). In addition, we measured the near-surface seawater concentrations of acetone, acetaldehyde, DMS and isoprene from a marine station 6 km offshore. Comparisons are made between EC fluxes from the open-water and bulk air–sea VOC fluxes calculated using air and water concentrations with a two-layer (TL) model of gas transfer. The calculated TL fluxes agree with the EC measurements with respect to the directions and magnitudes of fluxes, implying that any recently proposed surface emissions of acetone and acetaldehyde would be within the propagated uncertainty of 2.6 µmol m−2 d −1. The computed transfer velocities of DMS, acetone and acetaldehyde from the EC fluxes and air and water concentrations are largely consistent with previous transfer velocity estimates from the open ocean. This suggests that wind, rather than bottom-driven turbulence and current velocity, is the main driver for gas exchange within the open-water sector at PPAO (depth of ∼ 20 m)