Are video display terminals a source of increased PCB concentration in the working atmosphere?

Summary In response to the question: Are datascreen terminals a source of increased PCB concentrations in the working atmosphere? a study of PCB emissions from video display terminals (VDT) was undertaken. Emissions of 2.4 to 8.1 ng PCB/h were observed from VDT located in a building (1) where the mean PCB level in the air was 46 ng PCB/m³ during the test period, whereas no PCB emissions were detected from VDT located in a building (2) where no PCB could be detected in the ambient air. However, both the air and the VDT from building 2 were found to be contaminated with polycyclic aromatic hydrocarbons. We conclude that the observed PCB emissions from VDT are the result of the vapourization of PCB deposited onto the VDT from the PCB contaminated air and do not originate from the electrical components of the VDT.     

Exon identity influences splicing induced by exonic variants and in silico prediction efficacy

BackgroundMinigenes and in silico prediction tools are commonly used to assess the impact on splicing of CFTR variants. Exon skipping is often neglected though it could impact the efficacy of targeted therapies. The aim of the study was to identify exon skipping associated with CFTR variants and to evaluate in silico predictions of seven freely available software.MethodsCFTR basal exon skipping was evaluated on endogenous mRNA extracted from non-CF nasal cells and on two CFTR minigene banks. In silico tools and minigene systems were used to evaluate the impact of CFTR exonic variants on exon skipping.ResultsData showed that out of 65 CFTR variants tested, 26 enhanced exon skipping and that in silico prediction efficacy was of 50%-66%. Some in silico tools presented predictions with a bias towards the occurrence of splicing events while others presented a bias towards the absence of splicing events (non-detection including true negatives and false negatives). Classification of exons depending on their basal exon skipping level increased prediction rates up to 80%.ConclusionThis study indicates that taking basal exon skipping into account could orientate the choice of the in silico tools to improve prediction rates. It also highlights the need to validate effects using in vitro assays or mRNA studies in patients. Eventually, it shows that variant-guided therapy should also target exon skipping associated with variants.     

Optimal donation of kidney transplants after controlled circulatory death

Controlled donation after circulatory death (cDCD) is used for “extended criteria” donors with poorer kidney transplant outcomes. The French cDCD program started in 2015 and is characterized by normothermic regional perfusion, hypothermic machine perfusion, and short cold ischemia time. We compared the outcomes of kidney transplantation from cDCD and brain-dead (DBD) donors, matching cDCD and DBD kidney transplants by propensity scoring for donor and recipient characteristics. The matching process retained 442 of 499 cDCD and 809 of 6185 DBD transplantations. The DGF rate was 20% in cDCD recipients compared with 28% in DBD recipients (adjusted relative risk [aRR], 1.43; 95% confidence interval [CI] 1.12–1.82). When DBD transplants were ranked by cold ischemia time and machine perfusion use and compared with cDCD transplants, the aRR of DGF was higher for DBD transplants without machine perfusion, regardless of the cold ischemia time (aRR with cold ischemia time <18 h, 1.57; 95% CI 1.20–2.03, vs aRR with cold ischemia time ≥18 h, 1.79; 95% CI 1.31–2.44). The 1-year graft survival rate was similar in both groups. Early outcome was better for kidney transplants from cDCD than from matched DBD transplants with this French protocol.     

Activation of AMP-activated protein kinase in the liver: a new strategy for the management of metabolic hepatic disorders

It is now becoming evident that the liver has an important role in the control of whole body metabolism of energy nutrients. In this review, we focus on recent findings showing that AMP-activated protein kinase (AMPK) plays a major role in the control of hepatic metabolism. AMPK integrates nutritional and hormonal signals to promote energy balance by switching on catabolic pathways and switching off ATP-consuming pathways, both by short-term effects on phosphorylation of regulatory proteins and by long-term effects on gene expression. Activation of AMPK in the liver leads to the stimulation of fatty acid oxidation and inhibition of lipogenesis, glucose production and protein synthesis. Medical interest in the AMPK system has recently increased with the demonstration that AMPK could mediate some of the effects of the fat cell-derived adiponectin and the antidiabetic drugs metformin and thiazolidinediones. These findings reinforce the idea that pharmacological activation of AMPK may provide, through signalling and metabolic and gene expression effects, a new strategy for the management of metabolic hepatic disorders linked to type 2 diabetes and obesity.     

Computerized photo-plethysmography of the finger

A microcomputer system for studying photo-plethysmography of the finger (PPF) was designed and applied to 50 non-premedicated healthy boys (one to ten years old) undergoing general anaesthesia (halothane in 70% N₂O, with mechanical ventilation) for outpatient inguinal hernia repair. The purpose of this study was to assess the accuracy of computerized estimations of the photo-plethysmographic (arterial waves) amplitude and to evaluate whether or not PPF allows discrimination between two different surgical stimuli (skin incision, and manipulation of the spermatic cord). When anaesthesia was stable for at least five minutes (end-tidal halothane=1.25–1.5%;PetCO₂=32–38 mmHg; SpO₂≥98%; rectal temperature=36.3–37°C; ambient operating room temperature=20–21°C), and immediately before the skin incision, computerized estimations of the photo-plethysmographic (arterial waves) amplitudes (PPA) were recorded and saved for later comparison with direct (manual) measurements of the plethysmographic tracing, using an arbitrary scale of 0–255 units. Also, the values of PPA, systolic blood pressure, and pulse rate recorded immediately before the skin incision were later compared with the maximum changes in these same values recorded 30–90 sec after skin incision, and 30–90 sec after manipulation (traction + dissection) of the spermatic cord. Six boys (three to ten years old) stayed quiet enough, during induction of anaesthesia by mask, to allow regression analysis of PPA, systolic blood pressure, and pulse rate (Y) on end-tidal halothane/70% N₂O (X). Computerized estimations tended to give a higher reading, by between 0.2 to 0.8 units, than direct measurements. Spearman and Kendall correlations showed that computerized and direct measurements were associated (P<0.0001), the Kolmogorov-Smirnov’s test revealed that the two distributions were identical (P=1), the mean difference between computerized and direct estimations of the PPA was 0.52±1.08 units, and the limits of agreement (?1.6 and 2.6 units) were small enough to be confident that computerized (automatic) estimations of PPA can be used for clinical purposes. Skin incision caused a smaller decrease of PPA (24%) than manipulation of the spermatic cord (37%). Changes in PPA were more pronounced than changes in systolic blood pressure or pulse rate (P<0.05). Linear regressions and Fisher’s exact test (two-tailed) showed that, during induction of anaesthesia with halothane in 70% N₂O by mask (n=6), changes in end-tidal halothane concentration were related more to changes in PPA than to changes in systolic blood pressure and/or in pulse rate (P<0.05). In conclusion, computerized PPF allows discrimination between two different surgical stimuli, provides quantification of the sympathetic response to preoperative anxiety, and may be useful for studying pre-anaesthetic sedation.     

Behavioral and psychological symptoms in Alzheimer's disease. Relation between apathy and regional cerebral perfusion

Fundamental and therapeutic research in Alzheimer's disease (AD) focused for a long time exclusively on cognitive aspects. However, AD also frequently involves complex disorders of affect and behavior, which are currently grouped under the heading 'behavioral and psychological signs and symptoms of dementia' (BPSSD). Several rating tools have been developed over the years on the basis of a variety of source data. Some are derived from psychiatric practise or have specifically been developed for dementia, such as the Neuropsychiatric Inventory (NPI). In this study we prospectively used the NPI to examine BPSSD. Sixty-three French patients (mean age 74.7 years, SD 7.9) with a Mini-Mental State Examination (MMSE) score higher than 10 were examined. BPPSD were detected by NPI in 95. 2% of the patients. Anxiety was the most common abnormality (65.1%), followed by apathy and dysphoria (58.7%). The highest frequency x severity NPI score was observed for apathy. In order to identify the relationship between regional cerebral perfusion and apathy, 20 of these AD patients underwent a technetium-99m-bicisate SPECT protocol within the same week as the NPI evaluation. The mean age of this population was 74.4 years (SD 5.3) and the mean MMSE score was 21 (SD 4.1). The apathy NPI score was correlated with right cingulate deficit whereas the highest correlation for the MMSE was with the left temporoparietal area. This stresses the interest to focus on SPECT imaging of AD patients not only in the posterior areas. CopyrightCopyright 1999S.KargerAG,Basel     

Technetium-99m sestamibi imaging in paediatric neuroblastoma and ganglioneuroma and its relation to P-glycoprotein

Imaging with technetium-99m sestamibi offers a non-invasive approach to detect the presence of functional P-glycoprotein (Pgp), one of the major causes of multidrug resistance, in human malignancies. A clinical role for Pgp has been suggested in the subpopulation of primary neuroblastoma without amplification of the proto-oncogene MYCN. We wanted to evaluate the usefulness of 99mTc-sestamibi scintigraphy in the screening of neural crest tumours for the presence of Pgp. In ten children suffering from MYCN-negative neuroblastoma, ganglioneuroblastoma or ganglioneuroma, 99mTc-sestamibi imaging was performed at initial diagnosis. All patients underwent planar imaging 20-30 min and 3.5-4 h after intravenous injection of 740 MBq/1.73 m2 99mTc-sestamibi. Tumour to normal tissue ratios, as well as washout rates, were determined and compared with in vitro flow cytometric analysis of Pgp expression and function. Pgp expression was analysed flow cytometrically with the monoclonal antibodies 4E3 and MRK16, and Pgp function was evaluated by means of rhodamine 123 uptake and efflux either in the absence or in the presence of the Pgp inhibitor verapamil. In nine of ten patients, we found that the intratumoral 99mTc-sestamibi activity was comparable to the background activity, which might be suggestive of Pgp presence. This was confirmed flow cytometrically in all but one patient. 99mTc-sestamibi enhancement was seen in the primary tumour and the bone marrow metastases of one of the ten patients, and this result was concordant with a negative Pgp status. The findings presented suggest that 99mTc-sestamibi imaging results might correlate with the presence of functional Pgp in neural crest tumours without MYCN amplification.