CD40L is selectively expressed on platelets from thrombocytopenic septic patients

Introduction It has been recently hypothesized that septic microangio- pathy is caused or at least promoted by the interaction between endo- thelial surface receptor CD40 and its ligand CD40L, expressed by activated platelets. This interaction produces procoagulative changes in endothelial cells, endothelial apoptosis, subendothelial matrix exposition and microthrombi formation. Since virtually all septic patients show a certain degree of coagulation abnormalities, we hypothesized that low platelet count is associated with a diff erent degree of CD40L expression and that this could correlate with the severity of disease. Methods To determine the infl uence of sepsis on levels of platelet-derived CD40L expression, we performed a prospective observational study in a polyvalent university hospital ICU. Eighteen consecutively septic patients were enrolled in the study, independently of the platelet count and the severity of disease (SOFA score). Flow cytometry of fresh blood from septic patients (n = 18) and age-matched controls (n = 8) was performed for membrane-bound CD40L and CD62P on circulating platelets. Results Flow cytometry demonstrated low levels of CD62P in controls while the levels in patients were high. CD40L+ platelets were selectively found from patients with thrombocytopenia (platelet count ≤60,000/mm3). Furthermore a direct correlation between CD40L expression and the SOFA score was found in patients with sepsis and thrombocytopenia compared to patients with sepsis without thrombocytopenia. Conclusions These results suggest that CD40L expression on platelets is somehow related to the degree of thrombocytopenia and possibly can be a marker of the severity of sepsis. Although the role of endothelial- derived CD40/platelet-derived CD40L interaction is not fully understood during sepsis, the expression of CD40L on platelets could be related to the severity of organ disease due to the possible bursting of endothelial damage through this pathway. Further investigation is needed to determine whether platelets CD40L contributes to endothelial and subsequent organ damage, its role in thrombocytopenia and its correlation with the outcome of sepsis. The microvascular injury seems to be a central event in sepsis, so understanding the mechanisms underlying its development is crucial for the individuation of new and specifi c therapeutic strategies

Electroanalytical thread-device for estriol determination using screen-printed carbon electrodes modified with carbon nanotubes

Microflow systems are powerful analytical tools that explore similar principles of typical flow injection analysis driven to in a microfluidic device. Generally, microfluidic devices can promote a low consumption of reagents and samples, high speed of analysis and possibility of portability. Several advances have been reached applying a simple and low cost device based on cotton thread as microfluidic channel where the transportation of solutions is based on capillary force helped by gravity. In the present work, we have demonstrated the versatility of thread-based electroanalytical devices (μTED) constructed using a cotton thread as the solution channel and screen-printed electrodes (SPE) surface modified with carbon nanotubes (CNT) as electrochemical detectors for the amperometric determination of estriol hormone in pharmaceutical samples. The parameters involved in the amperometric detection and microflow system were studied and optimized, using the best experimental conditions (flow rate of 0.50 μL s−1, 10 mm of analytical path, 2.0 μL of volume of injection and potential of detection of 0.75 V) a linear response was observed for concentration range (LDR) of 1.0 to 1000 μmol L−1 with limits of detection (LOD) and quantification (LOQ) of 0.53 μmolL−1 and 1.77 μmolL−1, respectively, and frequency of injection of 32 per hour. The proposed methodology was applied for determination of estriol in commercial samples and results were compared with those provided by spectrophotometric method (official methodology). The obtained results are in agreement at a 95% of confidence level

Combination of electrochemical biosensor and textile threads: A microfluidic device for phenol determination in tap water

© 2017 Elsevier B.V. Microfluidic devices constructed using low cost materials presents as alternative for conventional flow analysis systems because they provide advantages as low consumption of reagents and samples, high speed of analysis, possibility of portability and the easiness of construction and maintenance. Herein, is described for the first time the use of an electrochemical biosensor for phenol detection combined with a very simple and efficient microfluidic device based on commercial textile threads. Taking advantages of capillary phenomena and gravity forces, the solution transportation is promoted without any external forces or injection pump. Screen printed electrodes were modified with carbon nanotubes/gold nanoparticles followed by covalent binding of tyrosinase. After the biosensor electrochemical characterization by cyclic voltammetry technique, the optimization of relevant parameters such as pH, potential of detection and linear range for the biosensor performance was carried out; the system was evaluated for analytical phenol detection presenting limit of detection and limit of quantification 2.94 nmol L −1 and 8.92 nmol L −1 respectively. The proposed system was applied on phenol addition and recovery studies in drinking water, obtaining recoveries rates between 90% and 110%

Dolichol: A Component of the Cellular Antioxidant Machinery

Dolichol, an end product of the mevalonate pathway, has been proposed a biomarker of aging, but its biological role, not to mention its catabolism, has not been fully understood. UV-B radiation was used to induce oxidative stress in isolated rat hepatocytes by the collagenase method. Effects on dolichol, phospholipids-bound polyunsaturated fatty acids (PL PUFA) and known lipid soluble antioxidants [coenzyme Q (CoQ) and α-tocopherol] were studied. The increase in oxidative stress was detected by a probe sensitive to reactive oxygen species (ROS). Peroxidation of lipids was assessed by measuring the release of thiobarbituric acid reactive substances (TBARS). Dolichol, CoQ and α-tocopherol were assessed by high-pressure liquid chromatography (HPLC), PL PUFA by gas-liquid chromatography (GC). UV-B radiation caused an immediate increase in ROS as well as lipid peroxidation and a simultaneous decrease in the levels of dolichol and lipid soluble antioxidants. Decrease in dolichol paralleled changes in CoQ levels and was smaller than that in α-tocopherol. The addition of mevinolin, a competitive inhibitor of the enzyme 3-hydroxy-3-methylglutaryl CoA reductase (HMG-CoAR), magnified the loss of dolichol and was associated with an increase in TBARS production. Changes in PL PUFA were minor. These findings highlight that oxidative stress has very early and similar effects on dolichol and lipid soluble antioxidants. Lower levels of dolichol are associated with enhanced peroxidation of lipids, which suggest that dolichol may have a protective role in the antioxidant machinery of cell membranes and perhaps be a key to understanding some adverse effects of statin therapy

Factors Associated with the Performance of a Blood-Based Interferon-γ Release Assay in Diagnosing Tuberculosis

Background: Indeterminate results are a recognised limitation of interferon-γ release assays (IGRA) in the diagnosis of latent tuberculosis (TB) infection (LTBI) and TB disease, especially in children. We investigated whether age and common co-morbidities were associated with IGRA performance in an unselected cohort of resettled refugees. Methods: A retrospective cross-sectional study of refugees presenting for their post-resettlement health assessment during 2006 and 2007. Refugees were investigated for prevalent infectious diseases, including TB, and for common nutritional deficiencies and haematological abnormalities as part of standard clinical screening protocols. Tuberculosis screening was performed by IGRA; QuantiFERON-TB Gold in 2006 and QuantiFERON-TBGold In-Tube in 2007. Results: Complete data were available on 1130 refugees, of whom 573 (51%) were children less than 17 years and 1041 (92%) were from sub-Saharan Africa. All individuals were HIV negative. A definitive IGRA result was obtained in 1004 (89%) refugees, 264 (26%) of which were positive; 256 (97%) had LTBI and 8 (3%) had TB disease. An indeterminate IGRA result was obtained in 126 (11%) refugees (all failed positive mitogen control). In multivariate analysis, younger age (linear OR = 0.93 [95% CI 0.91-0.95],

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

Cricoarytenoid arthritis as an early sign of juvenile chronic arthritis

A 14-month-old girl developed chronic strider and dyspnoea. Four months later she presented arthritis, anterior uveitis and positive ANA. Juvenile chronic arthritis (JCA) was diagnosed. Laryngoscopy demonstrated the presence of cricoarytenoid arthritis (CA). The left vocal cord was adducted and immobile, while the right vocal cord had decreased mobility. Erythema and swelling of the arytenoid cartilage on both sides was seen. Steroid treatment resulted in the resolution of these symptoms and made airway control unnecessary. This case demonstrates that CA may be the first sign of JCA, preceding peripheral arthritis. CA should be considered in, every child with chronic stridor and laryngeal obstruction

Extraction of a rubber bullet from a bronchus after 1 year - Complete resolution of chronic pulmonary damage

Inhalation of a foreign body (FB) into the bronchial tree rarely occurs asymptomatically and, if leading to recurrent pneumonia, can be very difficult to diagnose, The present report deals with the case of a 10-year-old boy who had three episodes of pneumonia in the left lower lobe caused by the asymptomatic inhalation of a FB 12 months before. Standard thoracic CT, done during the third episode, revealed a slight reduction in the volume of the left lung with air bronchograms, multiple areas of bronchiectasis, and parenchymal consolidation of a segment of the lower lobe, Flexible fiberoptic bronchoscopy revealed a FB at the distal end of the left lower lobar bronchus, surrounded by granulation tissue and fully obstructing the anterior basal segmental bronchus. High-resolution CT (HRCT) images showed an inverted C-shaped image obstructing a bronchus. Removal of the FB was successful only with rigid bronchoscopy under total anesthesia, The FB was an air-pistol rubber bullet that the boy remembered playing with 12 months before. Two months after removal of the FB (ie, 14 months from its asymptomatic inhalation) and treatment with oral steroids, antibiotics, and respiratory physiotherapy, the patient recovered completely, and HRCT showed complete normalization of the lung. We conclude that, when the radiographic density of the FB is greater than the surrounding pulmonary parenchyma, HRCT can reveal the FB, and diagnostic flexible fiberoptic bronchosopy can be avoided