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The use of catechol-O-methyltransferase inhibitors may mask doping agents, primarily levodopa, administered to racehorses and prolong the stimulating effects of dopaminergic compounds such as dopamine. It is known that 3-methoxytyramine is a metabolite of dopamine and 3-methoxytyrosine is a metabolite of levodopa thus these compounds are proposed to be potential biomarkers of interest. Previous research established a urinary threshold of 4,000 ng/mL for 3-methoxytyramine to monitor misuse of dopaminergic agents. However, there is no equivalent biomarker in plasma. To address this deficiency a rapid protein precipitation method was developed and validated to isolate target compounds from 100 µL equine plasma. A liquid chromatography-high resolution accurate mass (LC-HRAM) method using an IMTAKT Intrada amino acid column provided quantitative analysis of 3-methoxytyrosine (3-MTyr) with lower limit of quantification of 5 ng/mL. Reference population profiling (n = 1129) investigated the expected basal concentrations for raceday samples from equine athletes and showed a right-skewed distribution (skewness = 2.39, kurtosis = 10.65) which resulted from large variation (RSD = 71%) within the data. Logarithmic transformation of the data provided a normal distribution (skewness = 0.26, kurtosis = 3.23) resulting in the proposal of a conservative threshold for plasma 3-MTyr of 1,000 ng/mL at a 99.995% confidence level. A 12-horse administration study of Stalevo® (800 mg L-DOPA, 200 mg carbidopa, 1600 mg entacapone) revealed elevated 3-MTyr concentrations for 24-hours post-administration., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objectives: Late HIV diagnosis is associated with increased morbidity and mortality, increased risk of transmission, impaired response to antiretroviral therapy and increased health care costs. The aim of this study was to determine the factors associated with late HIV diagnosis in Grampian, North-East Scotland., Study Design: A population based retrospective database analysis., Methods: All newly diagnosed HIV positive individuals in Grampian, North-East Scotland between 2009 and 2014 were included in the study. Participants were classified as having a late diagnosis if the CD4 cell count at presentation was less than 350 cells/mm 3 . Socio-economic and demographic factors were investigated in relation to outcome (late diagnosis) using Chi-squared and Mann-Whitney tests., Results: CD4 cell count results were available for 111 (89.5%) of the 124 newly diagnosed individuals during the study period. The prevalence of late diagnosis was 53.2% (n = 59). Those infected via heterosexual mode of transmission had a 2.83 times higher odds of late diagnosis (OR 2.83 [95% CI: 1.10-7.32]) than men who have sex with men (MSM) and those with no previous HIV testing had a 5.46 increased odds of late diagnosis (OR 5.46 [95% CI: 1.89-15.81]) compared to those who had previously been tested. Missed opportunities for HIV diagnosis were identified in 16.3% (n = 15) of participants., Conclusion: Heterosexual individuals and those with no previous HIV testing were more likely to be diagnosed late. Targeted initiatives to increase perception of HIV risk and uptake of testing in these risk groups are recommended., (Copyright © 2016 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Background: We hypothesised that in blunt trauma patients with haemodynamic instability and haemoperitoneum on hospital admission, the haemorrhagic source may not be confined to the peritoneum. The purpose of this study was to describe the incidence and location of bleeding source in this population., Methods: The charts of trauma patients admitted consecutively between January 2005 and January 2010 to our level I Regional Trauma Centre were reviewed retrospectively. All hypotensive patients presenting a haemoperitoneum on admission were included. Hypotension was defined by a systolic blood pressure ≤ 90 mmHg. The haemoperitoneum was quantified on CT images or from operative reports as moderate (Federle score<3 or between 200 and 500 ml) or large (Federle score ≥ 3 or >500 ml). Active bleeding (AB) was defined as injury requiring a surgical or radiologic haemostatic procedure, regardless of origin (peritoneal (PAB) or extraperitoneal (EPAB))., Results: Of 1079 patients admitted for severe trauma, 110 patients met the inclusion criteria. Seventy-eight (71%) were male, mean age 35.3 (SD 19) years and mean ISS 36.5 (SD 20.5). Among the 91 patients who had AB, 37 patients (41%) had PAB, 34 (37%) had EPAB and 20 had both (22%). Forty-eight (53%) of them had moderate haemoperitoneum and 43 (47%) had large haemoperitoneum. A large haemoperitoneum had positive predictive value for PAB of 88% (95% CI 75-95%) and negative predictive value of 65% (95% CI 49-79%). The corresponding values in the subgroup of patients with EPAB were 65% (95% CI 38-86%) and 76% (95% CI 59-88%)., Conclusion: Haemoperitoneum was associated with PAB in only 52% of hypotensive blunt trauma patients and 63% of bleeding patients. In contrast, 59% of bleeding patients had at least one EPAB. The screening of a haemoperitoneum as a marker of active haemorrhagic source may be confusing and lead to misdiagnosis and inappropriate strategy. Clinician should exclude carefully the presence of any EPAB explaining haemorrhagic shock, before to decide haemostatic treatment., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Mucosal integrity may be objectively assessed by determination of the absorption of exogenous substances such as sucrose. Gas chromatography-mass spectrometry (GC/MS) and liquid chromatography-mass spectrometry (LC/MS) have been reported for the accurate quantification of low concentrations of sucrose in serum. LC/MS offered the advantage of high sensitivity and mass selectivity without the need for extensive sample derivatization required for GC/MS methods. However, the high polarity and non-volatile nature of the sucrose molecule renders LC/MS techniques challenging. Previously published reports lacked sufficient detail to permit replication of methodology. Problems encountered with existing protocols included poor peak resolution and weak fragmentation of the parent molecule. This communication describes a LC/MS protocol developed to provide improved resolution and product detection., (Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.)

Determining circulating equine insulin concentrations is becoming increasingly important in equine clinical practice and research. Most available assays are optimized for human medicine, but there is strong equine cross-reactivity because of the highly conserved nature of insulin. To identify an accurate and reliable assay for equine insulin, 6 commercial immunoassays were evaluated for precision, accuracy, and specificity. Only 1 assay initially reached the requisite standard: Mercodia Equine Insulin Enzyme-linked Immunosorbent assay (ELISA). Plasma matrix interferences were identified when the provided assay buffer was used with the Siemens Count-a-Coat Insulin radioimmunoassay (RIA) but not when charcoal-stripped equine plasma was used as the diluent. This modified RIA and the Mercodia Equine Insulin ELISA were evaluated further by directly examining accuracy by comparing their results for 18 equine plasma samples with values obtained using liquid chromatography and high-resolution/high-accuracy mass spectrometry (LC-MS). Compared with LC-MS measurements, the modified Siemens Insulin RIA rendered a moderate Lin's concordance coefficient (ρ(c)) of 0.41, whereas the Mercodia Equine Insulin ELISA rendered a very poor ρ(c) of 0.06. This suggests that the Siemens Insulin RIA is appropriate to use for routine evaluations when LC-MS is not available., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: To investigate health information needs of users of a health information website for children and young people., Methods: A prospective analysis was conducted of unsolicited information requests to the Children First for Health (www.childrenfirst.nhs.uk) website, an NHS-run health and hospital online information resource for children, young people and families. All specific and general enquiries were recorded prospectively and coded according to health topic, age of the enquirer and web pages accessed., Results: There were 2865 (62%) general health information and 924 (21%) specific enquiries received over an 18-month period (6.3 enquiries per day). More general enquiries were received about adolescent (64%) than children's (36%) health issues. The most common topics were psychosocial issues, hospital and health services, and normal growth and development. Only 1% of requests for information related to smoking, alcohol and drugs., Conclusion: Children and adolescents are active users of the Internet for health information. The results of this study highlight the health topics that are of greatest interest to children and young people., Practice Implications: The findings provide objective data on health information topics of interest to UK children and young people and can be used to guide development of health information aimed at UK youth.

LeuCAM (CD11/CD18) cell-surface antigens are easily upregulated on cell manipulation ex vivo. A procedure for preparing leucocytes, in which human blood is immediately treated ex vivo with buffered formaldehyde and then the erythrocytes and platelets are removed by lysis and differential centrifugation, has been successfully applied to the analysis of LeuCAM antigen expression by flow cytometry. We show that the increased expression of monocyte CD11/CD18, which occurs when mononuclear leucocytes are separated by a standard Lymphoprep density gradient separation, can be avoided if cells are fixed immediately. Following this fixation polymorphs are unable to upregulate CD11/CD18 in response to fMLP stimulation in vitro. The technique produces lymphocyte, polymorph and monocyte populations that can be clearly defined on the basis of forward scatter and side scatter, and preserves the expression of various surface antigens; the percentages of gated lymphocytes expressing CD3, CD4, and CD8 were similar to those obtained using a commercial fixing and lysis solution. The processing does not render cells permeable to antibodies, as evidenced by our failure to stain cells with antibodies to intracellular antigens. We believed the method to be useful for measuring CD11/CD18 expression on blood leucocytes from normal or pathological specimens and to have application to the measurement of other cells surface antigens which may also be upregulated by the separation procedures.

We propose an analytical model, which can simultaneously depict many fundamental characteristics of the immunogenicity of various vaccines. This model, the Immune Response (IR) profile, conveniently expresses the mathematical relation between pre- and post-vaccination titers. A vaccine's IR profile is antigen-specific, dose-dependent and post-vaccination interval-dependent. The maximal capability for serological response to a vaccine can be determined using this model irrespective of the dose administered, the post-vaccination assay interval, or the live or killed state of the vaccine. The IR profile obtained from analysis of booster vaccine responses in a limited number of seropositive study subjects can be used to predict maximal antibody titers which are expected after vaccination and can predict the geometric mean post-vaccination antibody titer of a cohort of subjects undergoing primary immunization. Using this model, it is anticipated that the immunoregulation implied by the IR profile may also prove to be correlated with cellular subpopulations and idiotypic antibody functions. Although derived from influenza vaccines analyses, the model successfully describes immune response characteristics following natural infection with malaria and following diphtheria and rubella vaccine administration.