Risk of Alzheimer's disease biological misdiagnosis linked to cerebrospinal collection tubes

Tau proteins and amyloid-β (Aβ) peptides are the current recognized cerebrospinal fluid (CSF) biomarkers used as an aid in the diagnosis of Alzheimer's disease (AD). However, there is no consensus on their clinical use due to non-qualified cut-off values, probably related to the observed high pre-analytical and analytical variability. Standardized pre-analytical protocols have therefore been proposed. Importantly, these recommend the use of polypropylene collection/sampling tubes while, to date, no broad comparison of these types of tubes has been conducted. In this study, we first compared, as part of a real clinical workflow, the impact of four different collection tubes on the CSF concentration of Aβ peptides (Aβ42, Aβ40) and total (hTau) and phosphorylated (P-Tau181P) tau proteins measured using routine ELISA kits. We then extended this study to 11 polypropylene tubes used by different clinical laboratories, and investigated their plastic polymer composition using differential scanning calorimetry and Fourier Transformed Infrared spectroscopy. Significant concentration variations linked solely to the use of different types of tubes were observed. This was particularly marked for Aβ peptides, with >50% disparity occurring in less than five minutes. Polymer composition analysis revealed that most polypropylene tubes were in fact copolymers with at least polyethylene. There was no clear correlation between tube composition and pre-analytical behavior. Our results show that the use of polypropylene tubes does not guarantee satisfactory pre-analytical behavior. They also point to collection/sampling tubes being a major pre-analytical source of variability that could impact the significance of AD biological diagnosis.     

Solvent-free hydrogenation of cyclohexene over Rh-TUD-1 at ambient conditions

Rhodium nanoparticles (≈3–5 nm) were incorporated into the 3D mesoporous TUD-1 material by using sol–gel technique. The prepared catalyst shows high activity in the liquid phase conversion of cyclohexene to cyclohexane at room temperature (298 K), 1 atm H₂ pressure, and under solvent-free conditions. Rhodium nanoparticles exhibited high stability, reusability and negligible leaching.

Total conversion of cyclohexene to cyclohexane was achieved in a liquid phase hydrogenation reaction at room temperature, 1 atm H₂ pressure and solvent-free system.     

Silent information regulator 1 protects the liver against ischemia–reperfusion injury: implications in steatotic liver ischemic preconditioning

Ischemia–reperfusion (IR) injury is an important problem in liver surgery especially when steatosis is present. Ischemic preconditioning (PC) is the only surgical strategy that has been applied in patients with steatotic livers undergoing warm ischemia. Silent information regulator 1 (SIRT1) is a histone deacetylase that regulates various cellular processes. This study evaluates the SIRT1 implication in PC in fatty livers. Homozygous (Ob) Zucker rats were subjected to IR and IR + PC. An additional group treated with sirtinol or EX527 (SIRT1 inhibitors) before PC was also realized. Liver injury and oxidative stress were evaluated. SIRT1 protein levels and activity, as well as other parameters involved in PC protective mechanisms (adenosine monophosphate protein kinase, eNOS, HSP70, MAP kinases, apoptosis), were also measured. We demonstrated that the protective effect of PC was due in part to SIRT1 induction, as SIRT1 inhibition resulted in increased liver injury and abolished the beneficial mechanisms of PC. In this study, we report for the first time that SIRT1 is involved in the protective mechanisms induced by hepatic PC in steatotic livers.     

Delayed Contrast-Enhanced MR Angiography for the Assessment of Internal Carotid Bulb Patency in the Context of Acute Ischemic Stroke: An Accuracy,Interrater, and Intrarater Agreement Study

BACKGROUND AND PURPOSE:CTA has shown limited accuracy and reliability in distinguishing tandem occlusions and pseudo-occlusions on initial acute stroke imaging. The utility of early and delayed contrast-enhanced MRA in this setting is unknown. We aimed to assess the accuracy and reliability of early and delayed contrast-enhanced MRA for carotid bulb patency in patients with acute ischemic stroke.MATERIALS AND METHODS:We retrospectively reviewed patients who had ICA occlusion and underwent thrombectomy with preprocedural early and delayed contrast-enhanced MRA in a single comprehensive stroke center. During 2 sessions, 10 raters independently assessed 32 cases with early contrast-enhanced MRA (with an additional delayed contrast-enhanced MRA sequence during the second reading session). Their judgments were compared with DSA as a reference standard. Accuracy and interrater agreement were measured. Five raters undertook a third reading session to assess intrarater agreement.RESULTS:Accuracy for the assessment of carotid bulb patency with early contrast-enhanced MRA was limited (69%; 95% CI, 59%–79%), with moderate interrater agreement (κ = 0.42; 95% CI, 0.27–0.55). The second reading with an additional delayed contrast-enhanced MRA sequence improved both accuracy (82%; 95% CI, 73%–91%; P < .001) (raters corrected 43%–77% of incorrect diagnoses with early contrast-enhanced MRA alone; mean = 59%) and interrater agreement (κ = 0.56; 95% CI, 0.41–0.73; P = .07). Intrarater agreement was almost perfect, substantial, and moderate for 3, 1, and 1 raters.CONCLUSIONS:Early contrast-enhanced MRA has limited accuracy and repeatability for the evaluation of carotid bulb patency in acute ischemic stroke. The additional delayed contrast-enhanced MRA sequence may improve accuracy and reliability.

Several trials have demonstrated the benefit of mechanical thrombectomy in acute ischemic stroke (AIS) with anterior circulation large-vessel occlusion¹ depicted by noninvasive intracranial vascular imaging (CTA or MRA). However, in case of tandem occlusion (ie, an ICA occlusion with an intracranial large-vessel occlusion), there remains uncertainty regarding the optimal management of the carotid bulb lesion,² and the benefits of acute angioplasty/stent placement are controversial.^3,4 Randomized controlled trials are needed to determine the best strategy and will thus require an accurate and repeatable noninvasive imaging method to select patients with an intracranial large-vessel occlusion and an additional carotid bulb occlusion,⁵ which will typically appear as an absence of visualization of the whole symptomatic carotid artery from the bulb.However, in AIS, a single, large clot located above the ICA bulb can impede contrast ascension from the common carotid artery, leading to a false image of bulbar occlusion, an entity called ICA pseudo-occlusion (PO).^6-9 It can, thus, be challenging to distinguish tandem occlusions and POs on initial acute stroke imaging. A previous study has shown limited accuracy and reliability of CTA for this task.¹⁰ CTA might thus be limited for the detection of tandem occlusions, whether in clinical routine (for endovascular management planning) or in research settings (for patient selection in a randomized controlled trial).MR imaging offers several interesting features for acute stroke imaging and decision-making, including a high sensitivity for the detection of early ischemic lesions¹¹ and the ability to detect stroke mimics¹² and identify patients who will benefit from reperfusion therapy in case of unknown onset stroke.¹³ Noninvasive vascular imaging can then be performed with MRA: The TOF sequence is usually performed for the depiction of intracranial large-vessel occlusion, and early contrast-enhanced MRA (CE-MRA), for the assessment of the complete supra-aortic vasculature. As with CTA, cases with an intraluminal filling defect of the bulb on ICA on the stroke side might correspond to either a tandem occlusion or a PO. Delayed acquisition after gadolinium injection (delayed CE-MRA) might overcome this issue, but CE-MRA performance has not been thoroughly studied in this setting.In this study, we aimed to assess the accuracy and reliability of early and delayed CE-MRA for the assessment of carotid bulb patency in patients with AIS.     

Drinking water nitrate and prevalence of methemoglobinemia among infants and children aged 1-7 years in Moroccan areas

ContextNitrate is ubiquitous in environmental media (air, water and soil) and other sources (some medicines, inorganic fertilizers and household's chemicals). It is a hemoglobin-oxidizing agent that can cause methemoglobinemia. The effect of nitrate on infants is well known but less is known about nitrate-induced methemoglobinemia in young children.MethodTwo cross-sectional studies were carried out in Salé, Morocco to determine the prevalence of methemoglobinemia among 411 infants and children aged 1–7 years in two adjacent areas that were similar in terms of the air quality, available vegetables and medicines but different in terms of the drinking water quality (nitrate-contaminated well water versus municipal water).ResultsIn the exposed area, nitrate concentration was measured in 78 wells and ranged from 15.39 to 246.90 mg/l as NO₃⁻. Nitrate levels were higher than 50 mg/l in 69.2% of the surveyed wells, and 64.2% of the participants were drinking nitrate contaminated well waters.The prevalence of methemoglobinemia among study children was 36.2% in the exposed area, and 27.4% in the non-exposed area. Study children drinking well water with a nitrate concentration >50 mg/l were significantly more likely to have methemoglobinemia than those drinking well water with a nitrate concentration <50 mg/l (p=0.001 at 95% CI=[1.22–2.64]) or than those drinking municipal water (p<0.01 at 95% CI=[1.16–2.21]). In the exposed area, the mean methemoglobin (MetHb) level increased with age (R²= 0.79, p=0.04), whereas in the unexposed area, the mean MetHb level remained relatively stable in the first 6 years of life (R²=0.21, p=0.44). Mean MetHb was normal when the nitrate concentration in water was below 50 mg/l as NO₃⁻, and reached an abnormal level, when the nitrate concentration in water ranged between 50 and 90 mg/l as NO₃⁻. This last level was statistically similar to mean MetHb at nitrate level above 90 mg/l as NO₃⁻ (up to 246.9 mg/l as NO₃⁻). No association was observed between methemoglobinemia prevalence and gender. This is the first study about methemoglobinemia conducted in Morocco.     

Hypoxia inducible factor-1�� accumulation in steatotic liver preservation: Role of nitric oxide

AIM:To examine the relevance of hypoxia inducible factor(HIF-1)and nitric oxide(NO)on the preservation of fatty liver against cold ischemia-reperfusion injury(IRI). METHODS:We used an isolated perfused rat liver model and we evaluated HIF-1αin steatotic and non-steatotic livers preserved for 24 h at 4℃in University of Wisconsin and IGL-1 solutions,and then subjected to 2 h of normothermic reperfusion.After normoxic reperfusion,liver enzymes,bile production,bromosulfophthalein clearance,as well as HIF-1αand ...     

Effect of IGL-1, a new preservation solution, on kidney grafts (a pre-clinical study)

Abstract Ischemia-reperfusion injury conditions short-term and long-term graft function. The effects of the inversion of K⁺ and Na⁺ concentrations and substitution with polyethylene glycol for hydroxyethyl starch in University of Wisconsin (K-UW) solution were evaluated in isolated perfused rat kidneys and in autotransplanted pig kidneys. In the rat model kidneys were cold-stored for 24 h in K-UW or Na-UW or Na-PEG UW solutions (IGL-1 solution). Fractional sodium reabsorption and glomerular filtration rate was better in kidneys preserved in Na-UW and IGL-1 solution than those preserved in K-UW solution. In the pig model the left kidney was harvested and preserved in K-UW or IGL-1 solution for 24 h and then transplanted. In the autotransplanted pig model, kidneys preserved in IGL-1 solution showed a better function and a significant reduction of MHC class II expression, cellular apoptosis and interstitial fibrosis. In conclusion, kidneys preserved in IGL-1 solution tolerated ischemia/ reperfusion injury better than those preserved in K-UW solution.     

Measurement of carbon monoxide in expired breath in prehospital management of carbon monoxide intoxication

INTRODUCTION: Carbon monoxide detectors are currently used by the French prehospital medical teams. These detectors can also be used to measure expired breath carbon monoxide concentration. The interest of this measurement has never been studied. OBJECTIVE: To evaluate interest of expired breath carbon monoxide concentration measurement in the management of prehospital carbon monoxide intoxication. STUDY DESIGN: Patients with carbon monoxide poisoning were included during 1998. PATIENTS AND METHODS: Four levels of clinical severity: no symptom, minor, medium or severe intoxication were defined. Carbon monoxide concentration were measured in the expired breath (COHbe) at the place of the intoxication and in blood samples collected at the place of the intoxication (COHbs) and at the hospital (COHbh). RESULTS: 209 patients were included, 144 had no symptom (55%), the value of COHbe was 11.6 +/- 7.5% (mean +/- DS) and the value of COHbh was 4.9 +/- 3.3%. 91 patients had minor intoxication (35%), the value of COHbe was 16.4 +/- 7.9% and the value of COHbh was 7.1 +/- 4.5%, 21 patients had sever or medium intoxication (8%) the value of COHbe was 26.4 +/- 17.7% and the the value of COHbh was 12.8 +/- 9.3%. Results for COHbh were obtained for only three patients. Relationship between symptoms and expired breath carbon monoxide and relationship between symptoms and carbon monoxide blood concentration on arrival at the hospital were significant (p < 0.05). CONCLUSION: Measurement of expired carbon monoxide concentration, easy and quick to perform is correlated with clinical severity in carbon monoxide poisoning.