Molecular variations to the proteome of zebrafish larvae induced by environmentally relevant copper concentrations.

Contaminants are increasingly accumulating in aquatic environments and biota, with potential adverse effects on individual organisms, communities and ecosystems. However, studies that explore the molecular changes in fish caused by environmentally relevant concentrations of metals, such as copper (Cu), are limited. This study uses embryos of the model organism zebrafish (Danio rerio) to investigate effect of Cu on the proteome and amino acid (AA) composition of fish. Wild-type embryos at 24 h post-fertilisation were exposed to Cu (2 µg L-1 to 120 µg L-1) for 96 h and the number of healthy larvae were determined based on larvae that had hatched and did not display loss of equilibrium (LOE). The effect concentrations where Cu caused a 10 % (EC10) or 50 % (EC50) decrease in the number of healthy larvae were calculated as 3.7 µg L-1 and 10.9 µg L-1, respectively. Proteomics analysis of embryos exposed to the EC10 and EC50 concentrations of Cu revealed the proteome to differ more strongly after 48 h than 96 h, suggesting the acclimatisation of some larvae. Exposure to excess Cu caused differentially expressed proteins (DEPs) involved in oxidative stress, mitochondrial respiration, and neural transduction as well as the modulation of the AAs (Proline, Glycine and Alanine). This is the first study to suggest that LOE displayed by Cu-stressed fish may involve the disruption to GABAergic proteins and the calcium-dependent inhibitory neurotransmitter GABA. Moreover, this study highlights that proteomics and AA analysis can be used to identify potential biomarkers for environmental monitoring.

Assessing alexithymia in adults with acquired brain injury: Psychometric properties of the Perth Alexithymia Questionnaire.

BACKGROUND: Alexithymia is a multidimensional personality trait comprised of difficulty identifying feelings, difficulty describing feelings, and externally orientated thinking. The assessment of alexithymia in people with acquired brain injury (ABI) is of clinical interest because alexithymia is linked to poor psychosocial functioning and community reintegration after ABI. To date, alexithymia measures have not been psychometrically investigated/validated in an ABI sample, restricting confident empirical work in this area. We aimed to fill this gap by assessing the psychometric properties of the Perth Alexithymia Questionnaire (PAQ) in adults with ABI and determining whether the alexithymia construct manifests similarly in ABI samples compared to the general community. METHODS: The PAQ and Depression Anxiety Stress Scales-21 were administered to an ABI sample (N = 350) and a community sample (N = 1012). Factor structure, measurement invariance, internal consistency reliability, and concurrent/discriminant validity were explored. RESULTS: Our confirmatory factor analysis of the PAQ supported the intended five-factor correlated model as the best solution, where items loaded well onto the five intended subscales. This factor structure was invariant across ABI and community samples. Good reliability and concurrent and discriminant validity were also established. LIMITATIONS: The PAQ is a self-report measure and may be impacted by insight deficits known to occur after ABI. CONCLUSION: Our data suggests that the PAQ has good validity and reliability as a measure of alexithymia. The latent structure of alexithymia manifests similarly in ABI and community samples. This study provides the first psychometric foundation for confident assessment of alexithymia in ABI.

Apathy and Depression as Predictors of Activities of Daily Living Following Stroke and Traumatic Brain Injuries in Adults: A Meta-Analysis.

Apathy and depression are common sequelae of acquired brain injury (ABI). Apathy is a syndrome characterized by diminished motivation and purposeful behaviours. Depression is a mood disorder featuring sadness, worthlessness, anhedonia and suicidal ideation. Both are associated negatively with activities of daily living (ADL), the skills required to fulfil basic and complex physical needs. However, the current literature's results are inconsistent and based on relatively small sample sizes. Furthermore, the unique and combined effects of apathy and depression as predictors of ADL have not yet been estimated. This is important, as both may have implications for planning rehabilitation after an ABI. Consequently, we aimed to estimate the association between apathy, depression and ADL in the stroke and traumatic brain injured population via meta-analysis and meta-analytic path-analysis. Based on the meta-analyses (N = 1,166 to N = 1,389), we estimated the following statistically significant bivariate effects: depression and apathy (r = .53, 95% CI: .42/.63), depression and ADL (r = -.27, 95% CI: -.43/-.11), apathy and ADL (r = -.41, 95% CI: -.51/-.31). A meta-analytic mediation model found that depression had a significant indirect effect onto ADL (ß = -.17, 95% CI: -.26/-.09), while apathy had a significant direct effect (ß = -.34, 95% CI: -.48/-.19) onto ADL (model R2 = .16). We interpreted the results to suggest that apathy and depression may impact adversely on engagement with ADL in people with ABI, although the potential influence of depression on ADL may occur primarily through its influence on apathy. Thus, greater focus on apathy by practitioners may be merited in cases with ABI.

Assessing cross-reactivity to neuromuscular blocking agents by skin and basophil activation tests in patients with neuromuscular blocking agent anaphylaxis.

BACKGROUND: Following diagnosis of neuromuscular blocking agent (NMBA) anaphylaxis, identifying safe alternatives for subsequent anaesthesia is critical. A patient with anaphylaxis to one NMBA can also have an allergic reaction to other NMBAs (cross-reactivity). Whilst drug provocation testing is standard for identifying or excluding allergy, there is significant risk. In vitro, after an allergen activates basophils, basophils express surface activation markers that can be measured by basophil activation testing (BAT). We compared cross-reactivity between NMBAs assessed by BAT against that by skin testing. METHODS: All patients attending an anaesthetic allergy clinic in Sydney, Australia between May 2017 and July 2018 diagnosed with NMBA anaphylaxis qualified for this study comparing intradermal skin tests and BAT with a panel of NMBAs (rocuronium, vecuronium, pancuronium, suxamethonium, cisatracurium). RESULTS: Of the 61 patients participating, sensitisation on skin testing and on BAT completely matched in only nine patients (15%). Sensitisation was not in agreement for pancuronium, cisatracurium and rocuronium, but was in agreement for vecuronium and suxamethonium. Nine patients with negative skin tests subsequently tolerated cisatracurium, and one false positive on BAT to cisatracurium was detected. CONCLUSIONS: The utility of BAT in identifying safe NMBAs for subsequent anaesthesia needs further evaluation. BAT detects a different cross-reactivity profile to skin tests. Negative skin testing and BAT might increase confidence in performing drug provocation testing, but this and follow-up of subsequent anaesthesia in our cohort is necessary to determine the clinical significance of BAT sensitisation.

Integrating basophil activation tests into evaluation of perioperative anaphylaxis to neuromuscular blocking agents.

BACKGROUND: Neuromuscular blocking agents (NMBAs) remain the leading cause of perioperative anaphylaxis in Australia. Standard evaluation comprises history, skin tests, and in vitro specific immunoglobulin E tests. Drug provocation tests to suspected NMBA culprits are associated with a significant risk. Basophil activation testing (BAT) is a potentially useful in vitro test that is not commercially available in Australia or as part of standard evaluation. METHODS: All patients attending the Anaesthetic Allergy Clinic in Sydney, Australia between May 2017 and July 2018 exposed to an NMBA before the onset of anaphylaxis during their anaesthetic qualified for the study. We recruited 120 patients sequentially who received standard evaluation plus BAT using CD63, CD203c, and CD300a as surface activation markers. RESULTS: BAT results were expressed as % upregulation above the negative control and stimulation index (mean fluorescence index of stimulated sample divided by the negative control). We calculated cut-offs of 4.45% and 1.44 for CD63, and 8.80% and 1.49 for CD203c, respectively. Sensitivity was 77% with specificity of 76%. A subgroup of 10 patients with NMBA anaphylaxis had no sensitisation on skin tests. BAT using CD63 and CD203c showed sensitisation in six of these 10, and adding CD300a identified sensitisation in nine patients. BAT was positive in seven of nine patients with anaphylaxis of unknown aetiology. CONCLUSIONS: BAT may be a useful supplement to the standard evaluation in diagnosing NMBA anaphylaxis in patients with suggestive histories, but no sensitisation on skin tests. Ongoing study of this specific group of patients is required to clarify its utility in clinical practice.