Rabbits are used as laboratory animal models and are also popular domestic pets. Allergic responses to rabbit allergens have been documented in both settings, and several rabbit allergens identified. ...We have purified an 18 kD protein extracted from rabbit fur that was shown by N-terminal sequencing and mass spectrometry (MS) to be a lipocalin, identical to that identified as an odorant binding protein and an allergen with the formal nomenclature of Ory c 1.
sequencing of the MS peptide fragments gave additional primary sequence data of this protein. Polyclonal antisera were raised against the purified protein and used to develop two types of immunoassay. Ory c 1 content was measured in used rabbit bedding and household dust samples from homes keeping rabbits as pets. Atmospheric sampling was also undertaken in an animal facility undertaking rabbit experimental work. Ory c 1 levels in house dust where rabbits were kept as pets were between undetectable-41,290 ng·g
, and in used bedding between 370-26,740 ng·g
. Significantly higher house dust levels were found where rabbits spent large amounts, or all of, their time indoors. Personal air sampler levels within the animal facility were between 65-216 ng·m
. Low levels (0.8-2 ng·m
) were found in the facility's changing rooms, but undetected in the entrance lobby, office and laundry. We believe that these immunochemical assays may be used to identify activities in the occupational and domestic setting which produce higher levels of exposure to rabbit allergens, and where measures to control exposure may be warranted to reduce potential risk of allergic outcomes.
Background
Image reconstruction and partial volume correction (PVC) techniques designed to account for the limited spatial resolution of PET are used inconsistently in amyloid and tau PET imaging, ...likely due to a lack of characterization of the techniques and their unknown effect on reliability. In this study, we aimed to test the accuracy and reliability of a variety of reconstruction and image‐based correction methods using 3D‐printed PET phantoms.
Method
Two phantoms modeled on the lateral temporal brain region of two human subjects (67‐year‐old male and 69‐year‐old female, both cognitively normal) were created using 3D‐printing technology (Formlabs Form 3). The phantoms had six thin‐walled chambers corresponding to inferior, middle, and superior temporal grey matter (GM) and white matter (WM). Phantoms were scanned (Siemens Biograph mCT) multiple times as chambers were filled with F‐18 solution to mimic various distributions of activity seen in amyloid‐positive, amyloid‐negative, or tau‐positive subjects. 16 scans were completed in total. Data from each 3‐hour scan were binned into 16 statistically equivalent frames and reconstructed with three techniques: FBP, OSEM, and TrueX, a manufacturer‐supplied method including point spread function modeling (Figure 1). Two image‐based correction techniques were also applied and evaluated: Geometric Mean Transfer Matrix (GTM) PVC and a novel Direct Regional Reprojection Reconstruction (DRRR) method, an iterative algorithm that reprojects images directly into regions‐of‐interest. To evaluate accuracy, fractional error of each region (F = M/T ‐ 1, where M is the measured regional value averaged over 16 frames and T is the true regional value) was calculated. To evaluate reliability, the coefficient of variation (CV) of M over all 16 frames in each scan was assessed for every region of the phantoms.
Result
Fractional errors (Figure 2) and CVs (Figure 3) are shown for each reconstruction and image‐based correction method. Uncorrected TrueX fractional error was not apparently improved relative to uncorrected FBP and OSEM fractional error. For all reconstructions, GTM and DRRR improved accuracy relative to uncorrected. For the FBP and OSEM reconstructions, GTM was more accurate than DRRR, but DRRR was more reliable than GTM.
Conclusion
DRRR is a promising novel method for PET quantification that improves accuracy without compromising reliability.
The processing of seafood (fish and shellfish) for human consumption can lead to health consequences, including occupational asthma (OA). Several non-UK studies have reported both respiratory ...outcomes and airborne levels of major allergens in seafood processing. However, there is a paucity of such evidence in the UK land-based seafood processing sector, which employs some 20 000 workers.
University of Manchester's Surveillance of Work-related and Occupational Respiratory Disease (SWORD) reporting system has been interrogated over the period 1992-2017 to define the incidence rate of OA cases that can be ascribed to the UK land-based processing sector, and the seafood species implicated. Airborne allergen monitoring data undertaken at Health and Safety Executive's laboratory from 2003 to 2019 have also been collated.
The estimated annual OA incidence rate in seafood processors was 70 95% confidence intervals (CIs) 48.9, 91.1 per 100 000 workers compared with 2.9 (95% CIs 2.8, 3.1) in 'all other industries'. The annual calculated percentage trend in OA (1992-2017) was -8.1% (95% CIs -15.9, 0.4) in seafood processing showing a similar trend to 'all other industries' (mean -7.0%; 95% CIs -7.8, -6.1). Prawns and salmon/trout were notably implicated by SWORD as causative species related to OA. There is a general paucity of available UK airborne allergen monitoring data, particularly concerning processing salmon or trout. Available airborne monitoring for salmon parvalbumin in seven processors ranged between the limit of detection and 816 ng m-3 (n = 64). Available air monitoring levels of the major shellfish allergen (tropomyosin) during processing of crabs and prawns ranged between 1 and 101 600 ng m-3 (n = 280), highlighting that high levels of exposure can occur.
These data show an excess incidence of OA in the UK seafood processing industry during 1992-2017, with limited airborne monitoring data for the processing of prawn, crab, and salmon suggesting that significant exposure to major seafood allergens can occur in this industry. Further investigation of current levels of respiratory ill-health and the sources of allergen exposure are warranted.
Exposure to laboratory animal allergens remains a significant cause of IgE-mediated occupational allergy and asthma. Since 2005, we have measured the major mouse and rat allergens (mus m 1 and rat n ...1) collected on filters from air sampling in a range of UK and non-UK animal facilities. Supplied core data allowed us to construct an anonymized database of atmospheric results in ng m–3 containing 3080 mouse and 1392 rat analyses. Roughly twice as many static samples compared to personal samples had been sent for analysis. The medians (90th percentiles) for the mouse and rat allergens employing personal atmospheric sampling were 2.6 (60.6) and 0.4 (12.4) ng m–3 respectively; for static samples the equivalent values were 0.2 (3.7) and 0.1 (1.4) ng m–3. Where unequivocal sample descriptors were provided with samples, results were categorised to activities/areas. Medians and 90th percentiles in these categories suggest that staff undertaking cleaning out, dumping of soiled bedding and cleaning cages can still have very substantial potential exposures in some facilities. The move to filtered cages appears to reduce general exposure, but filter changing and/or cleaning can lead to high exposures. In some facilities, animal receipt can cause significant exposures, as well as activities such as bleeding, culling and dosing; all activities involving the handling of animals outside of cages. We believe that the data presented may help those using air measurements in such facilities to improve their control of exposure to such aeroallergens, and thus reduce the risk of both sensitisation and subsequent allergic health problems, including the development of allergic asthma.
The role of specific cytochrome P450 isoforms in catalysing the oxidative biotransformation of the organophosphorothioate pesticides parathion, chlorpyrifos and diazinon into structures that inhibit ...cholinesterase has been investigated in human liver microsomes using chemical inhibitors. Pesticides were incubated with human liver microsomes and production of the anticholinergic oxon metabolite was investigated by the inhibition of human serum cholinesterase. Quinidine and ketoconazole at 10 μmol/l inhibited oxidative biotransformation. Compared to control incubations (no inhibitor) where cholinesterase activity was inhibited to between 1 and 4% of control levels, incorporation of the CYP2D6 inhibitor quinidine into the microsomal incubation resulted in cholinesterase activity of 50% for parathion, 38% for diazinon and 30% for chlorpyrifos. Addition of the CYP3A4 inhibitor ketoconazole to microsomal incubations resulted in 66% cholinesterase activity with diazinon, 20% with parathion and 5% with chlorpyrifos. The unexpected finding that CYP2D6, as well as CYP3A4, catalysed oxidative biotransformation was confirmed for chlorpyrifos and parathion using microsomes prepared from a human lymphoblastoid cell line expressing CYP2D6. While parathion has been investigated only as a model compound, chlorpyrifos and diazinon are both very important, widely used pesticides and CYP2D6 appears to be an important enzyme in their bioactivation pathway. CYP2D6 is polymorphic and hence may influence individual susceptibility to exposure to chlorpyrifos and diazinon as well as other structurally similar pesticides.
Magnetic resonance imaging (MRI) was used to monitor the displacement of refined oil by spontaneous imbibition of brine into fully oil-saturated cylindrical cores with either one end open (OEO) or ...two ends open (TEO) to flow. The rocks were outcrop Whitestone Upper Zone (UZ) limestone, Berea and a Bentheim sandstone/Rørdal chalk composite. In all cases, the wetting state was very strongly water-wet (VSWW). For OEO imbibition, high resolution imaging showed that brine invasion started at localized points and grew hemi-spherically outwards. The invaded regions increasingly overlapped until, after invasion of about one-third of the length of a standard core plug, a well-defined imbibition front formed that progessed as a remarkably sharp front at a velocity proportional to the square root of time. This behavior was usually observed for different boundary conditions and a range of permeabilities. For imbibition tests on a single core with TEO, imbibition started from the same core face no matter whether the core was horizontal, vertical or also vertical but inverted, showing that core heterogeneity dominated over the effect of gravity. The effect of heterogeneity was investigated further by imaging imbibition fronts in a TEO composite core formed from chalk butted against sandstone to provide a large difference in pore size. The fronts in the composite core moved at different times and velocities. Results are explained in terms of the capillary pressure gradients that develop within the composite core and, in particular, the capillary pressure at the open face(s). None of the behavior observed for a wide range of conditions can be modeled by the standard method which assumes relative permeabilities and capillary pressure relationships to give self similar fronts that expand as the front advances. The development of distinct fronts supports the modeling of imbibition, after the initial stages, as a piston-like displacement process.
Development of the advancing waterfront each open end face during TEO spontaneous imbibition into a composite core plug: chalk on the left, sandstone on the right. onset of imbibition started from localized points which grew hemi-spherically outwards from the open face followed by internal points of growth. Display omitted
► We image spontaneous imbibition in oil saturated cores at different conditions. ► Brine invasion started at localized points and grew hemi-spherically outwards. ► A defined front formed after invasion of a third of the length of a standard core. ► Core heterogeneity dominated over the effect of gravity where the front is developed. ► Front velocity is explained by capillary pressure gradient within heterogeneous cores.
Soya is an important bulk agricultural product often transported by sea as chipped beans and/or the bean husks after pelletisation. There are proven allergens in both forms. Bulk handling of soya ...imports can generate air pollution containing dust, allergens, and pyrogens, posing health risks to dockside workers and surrounding populations. Using an International Organization for Standardization (ISO) standardised rotating drum dustiness test in seven imported soya bulks, we compared the generated levels of dust and two major soya allergens in three particle sizes related to respiratory health. Extractable levels of allergen and endotoxin from the bulks showed 30–60 fold differences, with levels of one allergen (hydrophobic seed protein) and endotoxin higher in husk. The generated levels of dust and allergens in the three particle sizes also showed very wide variations between bulks, with aerolysed levels of allergen influenced by both the inherent dustiness and the extractable allergen in each bulk. Percentage allergen aerolysed from pelletized husk—often assumed to be of low dustiness—after transportation was not lower than that from chipped beans. Thus, not all soya bulks pose the same inhalation health risk and reinforces the importance of controlling dust generation from handling all soya bulk to as low as reasonably practicable.
Aims: To investigate the potential exposure to cytotoxic drugs of staff on two oncology wards in a large district, UK hospital under normal working conditions. Methods: Cytotoxic drug exposure was ...monitored in urine samples, surface wipes, and on disposable gloves by using a number of commonly used marker drugs, namely cyclophosphamide, ifosfamide, methotrexate, and the platino coordinated drugs. Questionnaire data on their work practices, potential exposure, use of protective personal equipment, and relevant training were collected from nursing, domestic, and clerical staff on two oncology wards. Results: The majority of staff were female with a mean age of 31 years. Roughly half of the staff studied were specifically trained nurses with an average of 3.5 years experience of administering cytotoxic drugs. No cytotoxic drug preparation or reconstitution was carried out on the wards. Disposable gloves, plastic armlets and aprons, but not eye protection, were invariably worn where there was potential exposure to cytotoxics. No cytotoxic drug was detected in any of the staff's urine samples. Isolated disposable latex gloves from nurses administering drugs showed some contamination, as did some surfaces within the wards' sluice rooms, but not in the ward areas where the drugs were stored and checked prior to administration. Conclusions: The risk management strategies in place, including use of personal protective equipment, staff training, and other organisational measures, have ensured that internal exposure is lower than the detection limits for the current biological monitoring methods. Levels of contamination appear significantly lower than earlier, non-UK published studies where different risk management strategies were in place and, in particular, ward staff may have been involved in some degree of cytotoxic drug reconstitution.
Bakers have a continuing high incidence of occupational allergic asthma. In factory bakeries they are exposed not only to flour dust containing allergens, but also improvers whose ingredients enhance ...the strength and workability of the dough and its speed of rising. Improvers are flour-based but can contain added soya, fungal or bacterial enzymes that are also allergenic, as well as vegetable oil, calcium sulphate/silicate and organic esters. This study investigated the dustiness of the components used in factory bakeries and whether altering improver ingredients could reduce dust and allergen exposure. A standardised rotating drum test was employed on the individual components, as well as a representative improver and three practicable improver modifications by decreasing calcium sulphate, calcium silicate or increasing oil content. Levels of dust, the allergens wheat flour amylase inhibitor (WAAI) and soya trypsin inhibitor (STI) were measured in the generated inhalable, thoracic and respirable sized fractions. A “scooping and pouring” workplace simulation was also performed. Initial tests showed that dustiness of several wheat flours was relatively low, and even lower for soya flour, but increased in combination with some other improver components. All three improver modifications generally reduced levels of dust, STI and WAAI, but increasing oil content significantly decreased dust and STI in comparison to the standard improver and those improvers with reduced calcium silicate or sulphate. The simulation demonstrated that increased oil content reduced inhalable levels of gravimetric dust, STI and WAAI. Changing improver formulation, such as increasing oil content of flour by a small amount, may represent a simple, practical method of reducing bakery workers’ exposure to dust and allergens where improvers are used. It may be a useful adjunct to engineering control, changes to work practices and appropriate training in reducing the risk to bakers’ respiratory health.