Mitochondrial dysfunction from malathion and chlorpyrifos exposure is associated with degeneration of GABAergic neurons in Caenorhabditis elegans

Toxicity resulting from off-target effects, beyond acetylcholine esterase inhibition, for the commonly used organophosphate (OP) insecticides chlorpyrifos (CPS) and malathion (MA) was investigated using Saccharomyces cerevisiae and Caenorhabditis elegans model systems. Mitochondrial damage and dysfunction were observed in yeast following exposure to CPS and MA, suggesting this organelle is a major target. In the C. elegans model, the mitochondrial unfolded protein response pathway showed the most robust induction from CPS and MA treatment among stress responses examined. GABAergic neurodegeneration was observed with CPS and MA exposure. Impaired movement observed in C. elegans exposed to CPS and MA may be the result of motor neuron damage. Our analysis suggests that stress from CPS and MA results in mitochondrial dysfunction, with GABAergic neurons sensitized to these effects. These findings may aid in the understanding of toxicity from CPS and MA from high concentration exposure leading to insecticide poisoning.     

Étude de faisabilité : l’utilisation de l’imagerie médicale en éducation thérapeutique en radiothérapie

PurposeAssess the feasibility of a randomized controlled trial (RCT) exploring the use of medical imaging as a therapeutic education (TPE) intervention in external radiation therapy.Materials and methodsExperimental feasibility trial of “RCT” type carried out in a single-center, between November 2019 and March 2020, following adult patients treated by thoracic radiotherapy. In addition to the information usually given, the experimental group benefited from an intervention consisting in the visualization of their own medical images using the open-source software “Stone of Orthanc”.ResultsForty-nine patients were recruited with a refusal rate of 8.16% (4/49). 20 patients were withdrawn from the study for health reasons (COVID), 10 for medical reasons. All the remaining 15 participants completed the process. Although not significant, the experimental group showed a median gain in the perception of knowledge compared to the control group (+ 1.9 (1.6 – 2.2)) vs (+ 1.4 (1.4 – 1.8)), as well as a decrease in scores related to anxiety (? 3.0 (?4.5 - (?2.0)) vs ? 1.0 (?5.0 - 0.0)) and emotional distress ((? 5.0 (? 7.5 - (? 3.5)) vs (? 2.0 (? 5.0 - (? 1.0)) A significant reduction (p = 0.043) is observed for the depression score ((? 2.0 (?3.0 - (?1.5)) vs (0.0 (0.0 – 0.0)).ConclusionThis study demonstrates the feasibility of the project, with promising preliminary results. Some adaptations in order to conduct a larger-scale RCT are highlighted.     

Trifluridine/Tipiracil in Combination with Bevacizumab in First-Line for Metastatic Colorectal Cancer: A Way Forward. A Point of View Based on Cost-Effectiveness

Introduction: The aim of this analysis is to assess the pharmacological costs of trifluridine/tipiracil as first-line treatment in metastatic colorectal cancer (mCRC) patients who were not candidates for combination with cytotoxic chemotherapies.Discussion: TASCO1 Trial was considered (153 patients). Differences in costs between the 2 arms (trifluridine/tipiracil plus bevacizumab vs. capecitabine plus bevacizumab) was 9113 € (10 264 USD), with a cost savings of 1982 € (2232 USD) per month of overall survival (OS)-gain.Conclusion: Trifluridine/tipiracil could be consider a cost-effective treatment also in first-line for mCRC patients who were not candidates for combination with cytotoxic chemotherapies.     

Diagnosing pulmonary thromboembolism: Concerns and controversies

Pulmonary thromboembolism (PTE) is an important cause of mortality/morbidity even today despite advancement in clinical understanding as well as diagnostic facilities. Clinical diagnosis of PTE is often challenging because of nonspecific sign/symptoms. Adherence to clinical decision-making protocols and appropriate use of diagnostic modalities like computed tomography pulmonary angiography can resolve the diagnostic dilemma in most cases and help in the overall management of PTE. This article deals with various concerns as well as controversies surrounding accurate diagnosis of PTE as on date.