HostSeq: a Canadian whole genome sequencing and clinical data resource.

HostSeq was launched in April 2020 as a national initiative to integrate whole genome sequencing data from 10,000 Canadians infected with SARS-CoV-2 with clinical information related to their disease experience. The mandate of HostSeq is to support the Canadian and international research communities in their efforts to understand the risk factors for disease and associated health outcomes and support the development of interventions such as vaccines and therapeutics. HostSeq is a collaboration among 13 independent epidemiological studies of SARS-CoV-2 across five provinces in Canada. Aggregated data collected by HostSeq are made available to the public through two data portals: a phenotype portal showing summaries of major variables and their distributions, and a variant search portal enabling queries in a genomic region. Individual-level data is available to the global research community for health research through a Data Access Agreement and Data Access Compliance Office approval. Here we provide an overview of the collective project design along with summary level information for HostSeq. We highlight several statistical considerations for researchers using the HostSeq platform regarding data aggregation, sampling mechanism, covariate adjustment, and X chromosome analysis. In addition to serving as a rich data source, the diversity of study designs, sample sizes, and research objectives among the participating studies provides unique opportunities for the research community.

Designing a couple-based relationship strengthening and health enhancing intervention for pregnant women living with HIV and their male partners in Zambia: Interview findings from the target community.

INTRODUCTION: Interpersonal support can promote positive outcomes among people living with HIV. In order to develop an acceptable psychoeducational couples-based intervention aimed at strengthening the relationship context and improving HIV outcomes before and after pregnancy, we conducted qualitative interviews with pregnant women living with HIV and their male partners. METHODS: We interviewed a convenience clinic-based sample of pregnant women living with HIV (n = 30) and male partners (n = 18) in Lusaka, Zambia. Interviews included pile sorting relationship topics in order of perceived priority. Interviews also focused on family health concerns. Interviews were audio-recorded, translated, transcribed, and thematically analyzed. Pile sorting data was analyzed using descriptive statistics. RESULTS: All female participants were living with HIV; 61% of the male partners interviewed were additionally living with HIV. The most prioritized relationship topic among both genders was communication between couples. Honesty and respect were important relationship topics but prioritized differently based on gender. Female participants considered emotional and instrumental support from male partners critical for their physical and mental health; men did not prioritize support. Intimate partner violence was discussed often by both genders. Family health priorities included good nutrition during pregnancy, preventing infant HIV infection, safe infant feeding, sexual health, and men's alcohol use. CONCLUSIONS: A major contribution of this study is a better understanding of the dyad-level factors pregnant women living with HIV and their male partners perceive to be the most important for a healthy, well-functioning relationship. This study additionally identified gaps in antenatal health education and the specific family health issues most prioritized by pregnant women living with HIV and their male partners. The findings of this study will inform the development of an acceptable couples-based intervention with greater likelihood of efficacy in strengthening the relationship context and promoting family health during and after pregnancies that are affected by HIV.

Group-based patient education delivered by nurses to meet a clinical standard for glaucoma information provision: the G-TRAIN feasibility study.

BACKGROUND: Globally, glaucoma is the leading cause of irreversible blindness. However, many patients with glaucoma do not understand their disease which reportedly impacts on their ability to manage their condition successfully. The aim of this feasibility study was to undertake research to inform a future randomised controlled trial of the effectiveness of group-based education for patients to improve adherence to glaucoma eyedrops. METHODS: Key objectives were to understand current provision of information during routine nurse-led glaucoma consultations, to investigate if it is possible to deliver patient information in line with a clinical standard by training nurses to deliver group-based education in multiple hospital sites and to explore the acceptability of group-based education to nurses and patients compared with usual information provision in consultations. This study employed quantitative and qualitative research methods situated in a sequential design across three hospitals in England and Wales. Current provision of information given to 112 patients with glaucoma across the three hospitals was observed and compared to that recommended in a clinical standard. Then, six nurses were trained to deliver group-based education. Following which, the level of information was assessed again in line with the clinical standard as the group-based education programme was delivered in the three hospitals to 16 patients in total. All nurses and six patients were interviewed to explore experiences of the group-based education sessions. RESULTS: The main area of information provided during routine nurse-led consultations concerned the management of glaucoma and that least covered was about prognosis of the disease and information about support services. Nurses were trained to implement group-based education for patients. Information was provided more often by the nurses about all the items of the clinical standard when delivering group based education. However, patients' motivation to attend were negatively impacted mainly by delays in delivering the education for the third phase and because the majority were established patients. Nurses and patients who participated found it useful and comprehensive. CONCLUSION: This feasibility study demonstrates that the proposed intervention for the randomised controlled trial, the group-based education, goes beyond current information provision, is in line with that articulated by a clinical standard and is implementable across several sites. This bodes well for a future randomised trial, but the following needs to be taken into account to ensure success: independent implementation of the research, training and delivery at each site, timely provision of the patient education, inclusion of new patients, and consistently delivered nurse training. TRIAL REGISTRATION: International Standard Randomised Controlled Trial number, ISRCTN91188805.

Tuning the Mechanical and Antimicrobial Performance of a Cu-Based Metallic Glass Composite through Cooling Rate Control and Annealing.

The influence of cooling rate on the wear and antimicrobial performance of a Cu52Z41Al7 (at. %) bulk metallic glass (BMG) composite was studied and the results compared to those of the annealed sample (850 °C for 48 h) and to pure copper. The aim of this basic research is to explore the potential use of the material in preventing the spread of infections. The cooling rate is controlled by changing the mould diameter (2 mm and 3 mm) upon suction casting and controlling the mould temperature (chiller on and off). For the highest cooling rate conditions CuZr is formed but CuZr2 starts to crystallise as the cooling rate decreases, resulting in an increase in the wear resistance and brittleness, as measured by scratch tests. A decrease in the cooling rate also increases the antimicrobial performance, as shown by different methodologies (European, American and Japanese standards). Annealing leads to the formation of new intermetallic phases (Cu10Zr7 and Cu2ZrAl) resulting in maximum scratch hardness and antimicrobial performance. However, the annealed sample corrodes during the antimicrobial tests (within 1 h of contact with broth). The antibacterial activity of copper was proved to be higher than that of any of the other materials tested but it exhibits very poor wear properties. Cu-rich BMG composites with optimised microstructure would be preferable for some applications where the durability requirements are higher than the antimicrobial needs.

Automation of route identification and optimisation based on data-mining and chemical intuition.

Data-mining of Reaxys and network analysis of the combined literature and in-house reactions set were used to generate multiple possible reaction routes to convert a bio-waste feedstock, limonene, into a pharmaceutical API, paracetamol. The network analysis of data provides a rich knowledge-base for generation of the initial reaction screening and development programme. Based on the literature and the in-house data, an overall flowsheet for the conversion of limonene to paracetamol was proposed. Each individual reaction-separation step in the sequence was simulated as a combination of the continuous flow and batch steps. The linear model generation methodology allowed us to identify the reaction steps requiring further chemical optimisation. The generated model can be used for global optimisation and generation of environmental and other performance indicators, such as cost indicators. However, the identified further challenge is to automate model generation to evolve optimal multi-step chemical routes and optimal process configurations.

Characterisation of non-toxigenic Clostridium spp. strains, to use as surrogates for non-proteolytic Clostridium botulinum in chilled food challenge testing.

Under many of the conditions studied, a two-strain cocktail of non-toxigenic Clostridium spp. was found to be suitable as a surrogate for non-proteolytic Clostridium botulinum, and has the potential for use in chilled food challenge tests measuring growth. Non-toxigenic surrogates could also be used in thermal process screening studies.

[Variety of the radial forearm phalloplasty with respect to urethral construction - a review]. / Varianten des Radialispenoids im Hinblick auf die Harnröhrenkonstruktion- Übersichtsarbeit.

SUMMARY: The radial forearm flap is an established procedure for phalloplasty. 3 different methods concerning flap design and urethral construction are reported in the literature. METHODS: A literature review between the years 1993 and 2012 was performed. The purpose of the review was an analysis of the different techniques of the radial forearm flap with respect to urethral construction in forming a phallus in female to male transsexual patients. Urological and flap specific complications were assed and compared between the methods. RESULTS: 9 studies with 714 patients were included into the analysis. One stage procedures for phalloplasty were performed in the majority of cases in 665 patients (93%). Among these 530 patients (74.2%) received a Chang design phallic construction. A 2 stage procedure with a prelaminated urethra was conducted in 49 patients (7%) and reported in 3 studies. CONCLUSION: The results show a higher rate of urological complications for the technique with urethra prefabrication so far. However, this technique presents with a lower incidence of partial flap loss and smaller donor sites compared to the Chang design phalloplasty. No conclusions can be drawn for the Gottlieb design penile construction because only few and incomplete data are available in the literature.

The prevalence of PFS and prevalence and characteristics of reported food allergy; a survey of UK adults aged 18-75 incorporating a validated PFS diagnostic questionnaire.

BACKGROUND: Pollen-food syndrome (PFS), a food allergy affecting pollen-sensitized individuals, is likely to be the most prevalent food allergy in adults, estimated to affect 50-90% of people allergic to birch tree pollen. OBJECTIVE: A validated PFS diagnostic questionnaire (PFSDQ2) was used to determine the prevalence of PFS and also to characterize those who report reactions to foods. METHODS: Five UK General practices each sent the PFSDQ2 by post to 2000 patients aged 18-75 years randomly selected from their practice database. The validated questionnaire was accompanied by an additional set of questions to ascertain the demographic of the population, the foods involved and the age of onset. RESULTS: There were 3590 subjects who returned completed questionnaires, with an average return rate from each practice of 36% (range 22-47%). Of these, 73 were diagnosed with PFS according to the questionnaire (PFS+ve) giving a population prevalence of 2%. A further 482 subjects reported reactions to foods but did not fulfil the diagnostic criteria for PFS. The greatest prevalence of PFS was in the Croydon (SE England) urban practice (4.1%) and the lowest in the Aberdeen (Scotland) urban practice (0.8%) (P < 0.001).The most frequently reported trigger foods were apples, hazelnuts and kiwifruit and the majority of those with PFS first experienced symptoms below the age of 20 years. PFS+ve subjects were also more likely to be female and have a higher socio-economic status than those who did not report reactions to foods. CONCLUSIONS: The UK prevalence of PFS was 2%, although this varied according to the location of the practice population. The majority of PFS+ve subjects first reported symptoms in their teens. The reported age of onset has important implications for the diagnosis of primary and cross-reactive peanut and tree nut allergies in teenagers and young adults. The continuing rise in aeroallergen sensitization is likely to result in an increased frequency of PFS presenting in both primary and secondary care.

Influence of season and geography on Campylobacter jejuni and C. coli subtypes in housed broiler flocks reared in Great Britain.

Geographical and seasonal variation in the incidence and prevalence of Campylobacter jejuni and C. coli in housed broiler flocks reared in Great Britain in 2004 to 2006 was investigated in this study. Ceca (30) from 797 flocks, not subject to prior partial depopulation and reared on 211 farms, were examined individually for the presence of Campylobacter spp. The best-fitting climatic factors explained approximately 46% of the prevalence of Campylobacter-colonized flocks at slaughter and consisted of a combination of temperature at slaughter, number of sunshine hours in placement month, and millimeters of rainfall in placement month. Positive flocks were more likely to be slaughtered between June and November than during the rest of the year and to be reared in northern Great Britain than in central or southern Great Britain. C. jejuni was identified in approximately 90% of flocks, and C. coli was present in 10% of flocks. The most common clonal complexes identified in 226 isolates typed by multilocus sequence typing (MLST) were ST-45, ST-21, ST-574, ST-443, and ST-828. Flocks slaughtered at the same time were more likely to have similar complexes, and ST-45 had a seasonal pattern, with the highest prevalence in June, and was also more likely to be present in flocks reared in northern Great Britain.

Kinetics of the homogeneous freezing of water.

Rates of homogeneous nucleation of ice in micrometre-sized water droplets are reported. Measurements were made using a new system in which droplets were supported on a hydrophobic substrate and their phase was monitored using optical microscopy as they were cooled at a controlled rate. Our nucleation rates are in agreement, given the quoted uncertainties, with the most recent literature data. However, the level of uncertainty in the rate of homogeneous freezing remains unacceptable given the importance of homogeneous nucleation to cloud formation in the Earth's atmosphere. We go on to use the most recent thermodynamic data for cubic ice (the metastable phase thought to nucleate from supercooled water) to estimate the interfacial energy of the cubic ice-supercooled water interface. We estimate a value of 20.8 +/- 1.2 mJ m(-2) in the temperature range 234.9-236.7 K.

Critical roles for the netrin receptor deleted in colorectal cancer in dopaminergic neuronal precursor migration, axon guidance, and axon arborization.

DCC (deleted in colorectal cancer), a receptor for the axon guidance cue netrin-1, is highly expressed by mesencephalic dopaminergic (DA) neurons during development; however, the contribution of DCC to DA development remains largely uncharacterized. DA neurons in ventral mesencephalic nuclei also express UNC5 homologue netrin receptors from late embryogenesis to adulthood, raising the possibility that DA axons could be attracted or repelled by netrins. Examining newborn dcc null mice, we report that loss of DCC function results in profound alterations of DA circuitry, including DA progenitor cell migration defects, reduced numbers of DA cells in midbrain nuclei, an anomalous DA ventral commissure, malformed DA innervation of the ventral striatum, and reduced DA innervation of the cerebral cortex. Caspase-3 activation was detected in inappropriately localized DA cells, consistent with apoptosis contributing to reduced cell numbers. Dcc heterozygous mice express reduced levels of DCC protein. Although less severely disrupted than dcc nulls, newborn and adult dcc heterozygotes also have fewer DA neurons in ventral mesenscephalic nuclei. Despite the reduced numbers of DA neurons, newborn dcc heterozygotes and nulls exhibit similar DA innervation density as wild-type littermates in the nucleus accumbens core, and adult dcc heterozygotes exhibit increased DA innervation in medial prefrontal cortex. A trend towards increased innervation of medial prefrontal cortex was detected in newborn dcc heterozygotes, but did not reach statistical significance, suggesting that the increase in adult heterozygotes results from enhanced DA arborization during postnatal development. Consistent with the hypothesis that DCC regulates DA axonal projections, disrupting DCC function in culture inhibits netrin-1 induced DA axon extension and axon branching. Furthermore, disrupting DCC function in isolated DA neurons grown as micro-island cultures reduces the number of autaptic synapses per cell. We conclude that DCC regulates appropriate precursor cell migration, axon guidance, and terminal arborization by DA neurons.

Nanomechanical characterization of tissue engineered bone grown on titanium alloy in vitro.

Intensive work has been performed on the characterization of the mechanical properties of mineralised tissues formed in vivo. However, the mechanical properties of bone-like tissue formed in vitro have rarely been characterised. Most research has either focused on compact cortical bone or cancellous bone, whilst leaving woven bone unaddressed. In this study, bone-like mineralised matrix was produced by osteoblasts cultured in vitro on the surface of titanium alloys. The volume of this tissue-engineered bone is so small that the conventional tensile tests or bending tests are implausible. Therefore, nanoindentation techniques which allow the characterization of the test material from the nanoscale to the microscale were adopted. These reveal the apparent elastic modulus and hardness of the calcospherulite crystals (a representative element for woven bone) are 2.35 +/- 0.73 and 0.41 +/- 0.15 GPa, respectively. The nanoscale viscoelasticity of such woven bone was further assessed by dynamic indentation analysis.

Using cancer registry data: agreement in cause-of-death data between the Ontario Cancer Registry and a longitudinal study of breast cancer patients.

Data from the Ontario Cancer Registry (OCR) were compared with data from a multi-centred prospective cohort of 1655 node-negative breast cancer patients with intensive clinical follow-up. Agreement in cause of death was evaluated using kappa statistics. The accuracy of OCR classification was evaluated against the Mount Sinai Hospital (MSH) study oncologist's interpretation of intensely followed, cohort-collected data as the reference standard. The two sources showed a high level of agreement (kappa statistic [kappa] = 0.88; 95% confidence interval [CI]: 0.86, 0.90) in vital status and cause of death. Among those cases where both sources reported a death, the OCR had a sensitivity of 95% (95% CI: 90.5, 98.8) and a specificity of 88% (95% CI: 79.6, 92.4). The OCR is a valuable tool for epidemiologic studies of breast cancer to acquire adequate and easily attainable cause-of-death information.

Agrobacterium-mediated transformation of friable embryogenic calli and regeneration of transgenic cassava.

Agrobacterium-mediated transformation of friable embryogenic calli (FEC) is the most widely used method to generate transgenic cassava plants. However, this approach has proven to be time-consuming and can lead to changes in the morphology and quality of FEC, influencing regeneration capacity and plant health. Here we present a comprehensive, reliable and improved protocol, taking approximately 6 months, that optimizes Agrobacterium-mediated transformation of FEC from cassava model cultivar TMS60444. We cocultivate the FEC with Agrobacterium directly on the propagation medium and adopt the extensive use of plastic mesh for easy and frequent transfer of material to new media. This minimizes stress to the FEC cultures and permits a finely balanced control of nutrients, hormones and antibiotics. A stepwise increase in antibiotic concentration for selection is also used after cocultivation with Agrobacterium to mature the transformed FEC before regeneration. The detailed information given here for each step should enable successful implementation of this technology in other laboratories, including those being established in developing countries where cassava is a staple crop.

Risk factors for Campylobacter colonisation during rearing of broiler flocks in Great Britain.

We investigated the associations between Campylobacter colonisation and management practices and farm characteristics in 603 housed broiler batches originating from 137 farms in Great Britain. All study batches were the initial batch slaughtered from the selected house on enrolled farms. Between 1 and 15 batches were sampled from each farm throughout the study. A total of 34.2% of the batches was Campylobacter positive and multivariable multilevel logistic regression revealed that the risk of Campylobacter colonisation was highest in July (OR=3.4, CI95%:1.8; 6.4), August (OR=3.4, CI95%:1.9; 6.2) and September (OR=3.7, CI95%:1.9; 7.1). Cattle on or adjacent to the farm increased the risk (OR=1.7, CI95%:1.1; 2.7), whereas chlorinated drinking water reduced it (OR=0.5, CI95%:0.2; 0.9). If the first removed batch from the previous flock in the house had been Campylobacter positive, the first batch of the following flock was also more likely to be colonised (OR=3.2, CI95%:2.1; 4.9). This association was more likely due to a persistent risk practice or source of Campylobacter on the farm than a direct carry-over from previous flock.

Campylobacter in housed broiler chickens: a longitudinal study of risk factors.

Infections by Campylobacter spp. are a major cause of gastrointestinal disease in the United Kingdom. Most cases are associated with the consumption of chicken that has become contaminated during production. We investigated the epidemiology of Campylobacter spp. in chickens in a 3-year longitudinal study of flocks reared on 30 farms in the United Kingdom. We used Generalized Linear Mixed Effect Models (GLMM) to investigate putative risk factors associated with incidence and prevalence of flock infection arising from farm and flock management and local environmental conditions during rearing. We used survival analysis to investigate infection events and associated risk factors over the course of the study using two marginal models - the independent increment approach, which assumed that individual infection events were independent; and a conditional approach, which assumed that events were conditional on those preceding. Models of flock prevalence were highly overdispersed suggesting that infection within flocks was aggregated. The key predictors of flock infection identified from the GLMM analyses were mean temperature and mean rainfall in the month of slaughter and also the presence of natural ventilation. Mean temperature in the month of slaughter was also a significant predictor of flock infection, although the analyses suggested that the risk in flocks increased in a unimodal way in relation to temperature, peaking at 12 degrees C. The extent of pad burn was also identified as a predictor in these analyses. We conclude that predicting prevalence within flocks with linear modelling approaches is likely to be difficult, but that it may be possible to predict when flocks are at risk of Campylobacter infection. This is a key first step in managing disease and reducing the risks posed to the human food chain.

Functional polymorphisms in the interleukin-6 and serotonin transporter genes, and depression and fatigue induced by interferon-alpha and ribavirin treatment.

Depression and fatigue are frequent side effects of interferon-alpha (IFN-alpha) treatment, and there is compelling evidence that the inflammatory response system (including interleukin-6, IL-6) and the serotonergic system is important in the pathophysiology of such symptoms. Functional polymorphisms in the promoter region of the IL-6 gene (rs1800795) and serotonin transporter gene (5-HTTLPR) have been identified as regulating these systems. The present study aimed to determine if these polymorphisms were associated with the development of depression and fatigue during IFN-alpha and ribavirin treatment. Ninety-eight Caucasian patients receiving pegylated IFN-alpha and ribavirin treatment for chronic hepatitis C virus at King's College Hospital, London, and Emory University Hospital, Atlanta, participated in this prospective cohort study. Symptoms of depression and fatigue were measured before treatment and at weeks 4, 8, 12 and 24 during treatment. The 'low IL-6' synthesizing genotype (CC) was associated with significantly fewer symptoms of depression (effect size = 0.7 at week 24; F = 9.4, d.f. = 436, P = 0.002). The 'high transcription' serotonin transporter (5-HTT) genotype (LL) was also associated with significantly fewer symptoms of depression, but with a much smaller effect (effect size = 0.2 at week 24; F = 4.5, d.f. = 436, P = 0.03). Neither polymorphisms were associated with symptoms of fatigue (IL-6: F = 1.2, d.f. = 430, P = 0.2; 5-HTT: F = 0.5, d.f. = 430, P = 0.5). The smaller effects of the 5-HTT polymorphism on depression may be explained by an interaction between the genes (F = 5.0, d.f. = 434, P = 0.02): the 'protective' effect of the 5-HTTLPR polymorphism was evident only in the presence of the 'low IL-6' genotype (F = 5.4, d.f. = 64, P = 0.02), not in the presence of the 'high IL-6' genotype (F = 2.2, d.f. = 369, P = 0.1). The association between the IL-6 polymorphism and reduced risk of depressive symptoms confirms the role of the inflammatory response system in the pathophysiology of IFN-alpha-induced depression; in contrast, the effect of the 5-HTT gene was small and perhaps dependent on the status of the inflammatory response.

Improving recruitment and retention for an online randomized controlled trial: experience from the Youthnet study.

The objective of the study was to present recruitment and retention findings for an Internet based HIV prevention trial evaluated using a randomized controlled design among 15-25-year-olds accessing a website on the Internet. We used a combination of automated electronic and personalized approaches to increase and diversify recruitment, verify participant eligibility and increase retention. We posted 3.5 million banner advertisements, 9354 individuals clicked on the advertisement, 8950 completed an eligibility screener and 3298 a baseline survey; we flagged 675 of these as suspicious and enrolled 2623 individuals. Of these, 2082 (79%) completed a follow-up at one-month and 1398 (53%) completed a two-month follow-up. This retention rate is the highest we have seen for an Internet-based HIV-prevention trial. Our procedures can be replicated in other trials. We stress the importance of using a combination of automated and personalized techniques to increase enrollment, verify eligibility and promote retention.

Factors affecting the incidence of genotoxicity biomarkers in peripheral blood lymphocytes: impact on design of biomonitoring studies.

A review of risk factors affecting background rates of micronuclei and chromosomal aberration (CA) formation in peripheral blood lymphocytes (PBLs) was undertaken with a view to aiding the interpretation of genotoxicity biomonitoring studies. Both endogenous factors and those due to methodological variation were evaluated. Background variation of other indices of genotoxicity in PBLs (specifically 8-hydroxy-deoxyguanosine and comet assays) were also considered as these data likely reflect overlapping causes of DNA damage and may provide some indicators for future research areas. A number of host risk factors, namely age, gender, smoking, vitamin B(12) and folate status, were identified for which there is strong or sufficient evidence that they impact on background levels of genotoxicity biomarkers. Evaluation of these factors should be routinely included in genotoxicity biomonitoring studies. Although data on the influence of smoking is somewhat inconsistent, because of its known association with cancer and DNA damage, it is also classified as a high-risk factor. A number of other factors were identified for which there is weak or insufficient evidence including alcohol consumption, disease conditions and infections, physical exercise, body mass index and genotype. The review shows that the evaluation of biomonitoring studies of genotoxicity is complex and there is a need to improve study designs by setting an a priori hypothesis, collecting good exposure data and stratifying groups appropriately, using appropriate power calculations before initiating biomonitoring studies, and collecting information on appropriate risk factors. There is a need for further collaborative work and the establishment of centres of excellence on genotoxicity biomonitoring. If these measures are achieved, then it would be possible to use the data from biomonitoring studies in risk assessments to derive risk management measures.

Differences in hepatic cytochrome P450 activity correlate with the strain-specific biotransformation of medetomidine in AX/JU and IIIVO/JU inbred rabbits.

Medetomidine is an alpha(2)-adrenoceptor agonist with sedative and analgesic properties. Previously we demonstrated significant differences in the response to medetomidine between two inbred rabbit strains, denoted IIIVO/JU and AX/JU. The aim of the present study was twofold: first, to compare the hepatic CYP450 enzyme activities between these rabbit strains [n = 13(male male,7 female female)/strain]. To this end, liver microsomes were incubated with known fluorescent substrates for the major drug-metabolizing CYP450 isoforms. A comparison of the obtained results indicated significant gender differences as well as differences between the two rabbit inbred strains. Secondly, the biotransformation rate of medetomidine in liver microsomes of both rabbit strains was determined using liquid chromatography coupled to tandem mass spectrometry. The rate of hydroxymedetomidine and medetomidine carboxylic acid formation was found to be significantly higher in the AX/JU strain. Specific CYP2D and CYP2E inhibitors could decrease the formation of both metabolites. Significant correlations were found between the rate of biotransformation of medetomidine and the activities of CYP2D and CYP2E, as well as between CYP450 enzyme activities and the anaesthetic response to medetomidine.