The use of portable XRF as a forensic geoscience non-destructive trace evidence tool for environmental and criminal investigations.

Hand-held, portable X-Ray fluorescence instruments (pXRF) provide a means of rapid, in-situ chemical characterisation that has considerable application as a rapid trace evidence characterisation tool in forensic geoscience. This study presents both a control test study which demonstrates optimisation of the data collection process, alongside a range of individual forensic case studies, including heavy metal contamination, conflict archaeology, forensic soil characterisation, and verification of human remains, which together validate the technique and provide some comparison between field-based and laboratory-based pXRF applications. Results highlight the time-efficiency and cost-effectiveness of in-situ, field-based pXRF analyses for material characterisation when compared with other trace evidence methods. Analytical precision of various analytes during in-situ analysis was sufficient to demonstrate considerable application of field-based pXRF as a tool for rapid identification of specific areas of interest to be further investigated. Laboratory-based pXRF analyses yielded greater accuracy which could provide an efficient compromise between field-based pXRF and traditional laboratory-based analytical techniques (e.g. WD-XRF, ICP-MS). Further studies should collect more advanced datasets in more diverse locations to further validate the techniques capability to rapidly conduct geochemical surveys in a range of environments.

L-alpha-amino adipic acid provokes depression-like behaviour and a stress related increase in dendritic spine density in the pre-limbic cortex and hippocampus in rodents.

Astrocyte dysfunction is implicated in clinical depression. There is a paucity of animal models to assess the role of astrocytes in depression pathogenesis. Refinement of an existing model is described here. Administration of the astrocytic toxin L-alpha aminoadipic acid (L-AAA) to the pre-limbic cortex (PLC) was assessed in rats and mice in tests of anxiety and depression related behaviours. Delivery of L-AAA to the PLC of Wistar rats produced an increase in immobility in the forced swimming test (FST) and reduced exploration in the open field. Delivery to the CA3 subfield of the hippocampus produced a deficit in the novel object relocation task. Delivery of single or two successive doses of L-AAA to the PLC of C57Bl6/J mice was sufficient to induce an increase in immobility in the mouse tail suspension (TST) and FST independently of administration of anaesthetic agent or the surgical procedure. In both mice and rats, L-AAA produced a reduction in immunoreactivity of the astrocytic marker glial fibrillary acidic protein (GFAP) for up to 72 h. L-AAA provoked an increase in the density of apical and basal dendritic spines in mice exposed to the FST when compared to non-FST controls. In summary, L-AAA provokes a region-dependent change in behaviour, a reduction in GFAP immunoreactivity and FST-provoked increased in dendritic spine density in the PLC. This model may be further employed to assess the impact of astroglial integrity on the structural plasticity of neurons and the effect of antidepressant agents on L-AAA-related changes.

Management of thoracic spine pain and dysfunction: A survey of clinical practice in the UK.

BACKGROUND: The thoracic spine (TS) is relatively under-researched compared to the neck and low back. As the challenge of managing spinal pain persists, understanding current physiotherapy clinical practice for TS pain and dysfunction is necessary to inform future research in this area. OBJECTIVE: To investigate physiotherapy practice for managing thoracic spine pain and dysfunction (TSPD) in the UK, with a secondary focus on examining differences across settings and expertise. DESIGN AND METHOD: A cross sectional e-survey informed by existing evidence was designed. Comprising closed and open questions, the survey is reported in line with Checklist for Reporting Results of Internet E-Surveys. Eligible participants were UK-trained physiotherapists managing patients with TSPD, recruited for 9 weeks up to 8/2/16. Data analysis included descriptive analyses (closed questions) and thematic analysis (open questions). RESULTS: From the 485 respondents, fulfilling the required sample size, key findings included. EXAMINATION: Active motion testing, palpation and postural assessment was 'always' undertaken by >89% of respondents. MANAGEMENT: Active (exercises) and passive (e.g. mobilisations) techniques were used by >85% of respondents, with ∼50% using manipulation, taping and acupuncture. Practice settings: Although broadly similar passive techniques were used more in private practice and sport. Expertise: Broadly similar patterns were seen for use of exercise across levels of expertise, although differences observed for electrotherapy and manipulation. CONCLUSION: Despite limited research exercise is widely used in all areas of practice and across all level of expertise. Further research is required to investigate exercise prescription for TSPD and implementation of evidence-based practice.

Investigation of the mechanisms mediating MDMA "Ecstasy"-induced increases in cerebro-cortical perfusion determined by btASL MRI.

RATIONALE: Acute administration of the recreational drug of abuse 3,4-methylenedioxymethamphetamine (MDMA; Ecstasy) has previously been shown to increase cerebro-cortical perfusion as determined by bolus-tracking arterial spin labelling (btASL) MRI. OBJECTIVES: The purpose of the current study was to assess the mechanisms mediating these changes following systemic administration of MDMA to rats. METHODS: Pharmacological manipulation of serotonergic, dopaminergic and nitrergic transmission was carried out to determine the mechanism of action of MDMA-induced increases in cortical perfusion using btASL MRI. RESULTS: Fenfluramine (10 mg/kg), like MDMA (20 mg/kg), increased cortical perfusion. Increased cortical perfusion was not obtained with the 5-HT2 receptor agonist 2,5-dimethoxy-4-iodophenyl-aminopropane hydrochloride (DOI) (1 mg/kg). Depletion of central 5-HT following systemic administration of the tryptophan hydroxylase inhibitor para-chlorophenylalanine (pCPA) produced effects similar to those observed with MDMA. Pre-treatment with the 5-HT receptor antagonist metergoline (4 mg/kg) or with the 5-HT reuptake inhibitor citalopram (30 mg/kg), however, failed to produce any effect alone or influence the response to MDMA. Pre-treatment with the dopamine D1 receptor antagonist SCH 23390 (1 mg/kg) failed to influence the changes in cortical perfusion obtained with MDMA. Treatment with the neuronal nitric oxide (NO) synthase inhibitor 7-nitroindazole (7-NI) (25 mg/kg) provoked no change in cerebral perfusion alone yet attenuated the MDMA-related increase in cortical perfusion. CONCLUSIONS: Cortical 5-HT depletion is associated with increases in perfusion although this mechanism alone does not account for MDMA-related changes. A role for NO, a key regulator of cerebrovascular perfusion, is implicated in MDMA-induced increases in cortical perfusion.

Plasma and urinary cytokine homeostasis and renal function during cardiac surgery without cardiopulmonary bypass.

Cardiopulmonary bypass (CPB) significantly contributes to the plasma pro-inflammatory cytokine response at cardiac surgery. Complementary plasma and urinary anti-inflammatory cytokine responses have been described. The pro-inflammatory cytokines interleukin 8 (IL-8), tumour necrosis factor alpha (TNF-alpha) and interleukin 1beta (IL-1beta) have lower molecular weights than the anti-inflammatory cytokines interleukin 10 (IL-10), interleukin 1 receptor antagonist (IL-1ra) and TNF soluble receptor 2 (TNFsr2) and thus undergo glomerular filtration more readily. In vitro work suggests that proximal tubular cells are vulnerable to pro-inflammatory cytokine mediated injury. Accordingly, this study investigated the hypothesis that cardiac surgery without CPB would not have significant changes in plasma and urinary cytokines and proximal renal dysfunction. Eight patients undergoing coronary artery bypass grafting (CABG) without CPB were studied. Blood and urine samples were analysed for pro- and anti-inflammatory cytokines. Proximal tubular dysfunction was measured using urinary Nu-acetyl-beta-D-glucosaminidase (NAG)/creatinine and alpha(1)-microglobulin/creatinine ratios. Plasma IL-8, IL-10, IL-1ra and TNFsr2 were significantly elevated compared with baseline. Urinary IL-1ra and TNFsr2 were significantly elevated, as were urinary NAG/creatinine and alpha(1)-microglobulin/creatinine ratios. Two hours following revascularization, urinary IL-1ra correlated with urinary alpha(1)-microglobulin/creatinine ratios (P<0.05). As previously reported in CABG surgery with CPB, we now report that non-CPB cardiac surgery also has significant changes in plasma and urinary cytokine homeostasis and early proximal tubular injury. The correlation between urinary IL-1ra and alpha(1)-microglobulin/creatinine ratios is consistent with earlier suggestions of a mechanistic link between cytokine changes and proximal tubular dysfunction. The relative roles of CPB and non-CPB processes in producing inflammation still require definition.

Plasma and urinary cytokine homeostasis and renal dysfunction during cardiac surgery.

BACKGROUND: Cardiac surgery induces changes in plasma cytokines. Proinflammatory cytokines have been associated with a number of renal diseases. The proinflammatory cytokines interleukin 8 (IL-8), tumor necrosis factor alpha (TNFalpha), and interleukin 1beta (IL-1beta) are smaller than the antiinflammatory cytokines interleukin 10 (IL-10), interleukin 1 receptor antagonist (IL-1ra), and TNF soluble receptor 2 (TNFsr2), and thus undergo glomerular filtration more readily. Accordingly, this study investigated the relation between plasma and urinary cytokines and proximal renal dysfunction during cardiac surgery. METHODS: Twenty patients undergoing coronary artery bypass grafting with cardiopulmonary bypass (CPB) were studied. Blood and urine samples were analyzed for proinflammatory and antiinflammatory cytokines. Proximal tubular dysfunction was measured using urinary N-acetyl-beta-d-glucosaminidase (NAG)/creatinine and alpha1-microglobulin/creatinine ratios. RESULTS: Plasma IL-8, IL-10, IL-1ra, and TNFsr2 values were significantly elevated compared with baseline. Urinary IL-1ra and TNFsr2 were significantly elevated. Urinary NAG/creatinine and alpha1-microglobulin/creatinine ratios were also elevated. Plasma TNFalpha at 2 h correlated with urinary NAG/creatinine ratio at 2 and 6 h (P < 0.05) and with urinary IL-1ra at 2 h (P < 0.05). Plasma IL-8 at 2 h correlated with NAG/creatinine at 6 h (P < 0.05). Urinary IL-1ra correlated with urinary NAG/creatinine ratio after cross-clamp release and 2 and 6 h after CPB (P < 0.05). CONCLUSIONS: Cardiac surgery using CPB leads to changes in plasma and urinary cytokine homeostasis that correlate with renal proximal tubular dysfunction. This dysfunction may be related to the renal filtration of proinflammatory mediators. Renal autoprotective mechanisms may involve the intrarenal generation of antiinflammatory cytokines.