Inflammasomes and Colorectal Cancers

Further agreements on the level of detail and uncertainty, robustness, predictive value, reproducibility and validation are a prerequisite to develop tools that can be trusted and that will be legally binding.Despite a continuous increase of commercial products containing nanoparticles, only few materials are currently used in such large amounts, forms and sizes as titanium dioxide - TiO2. Besides its use in cosmetics, food industry and biomedicine, TiO2 nanoparticles (NPs) are also used as highly efficient photocatalysts due to their unique ability to convert complex organic materials to carbon dioxide, water and simple mineral acids via complex radical and electron transfer reactions. The main objective of the current project was to assess the potential dermal effect (phototoxicity and skin toxicity) of TiO2 nanosheets (TIG-800) synthesized from the lyophilized aqueous colloids of peroxo-titanic acid by high-temperature treatment. The effect was examined on reconstructed human skin model EpiDerm in the test pre-validated by ECVAM and adopted into the ICH S10 guidelines for the preclinical photo-safety assessment of drugs. In addition, two further commercial samples of nanocrystalline TiO2, namely Aeroxide P25 and Eusolex T-2000, and six benchmark materials from pre-validation studies were tested. None of the TiO2 NPs tested in the study caused acute phototoxicity or cytotoxicity in the reconstructed 3D tissues up to the highest concentration tested. The prediction of photo-irritation potency for the benchmark chemicals was comparable to previous studies. For some of the tested materials, we identified reasons for false negative results or variability in previously published datasets by improved dosing, conditions of irradiation, and choice of suitable solvents. The method proved its suitability for photo-irritation assessment of topically applied materials.The first microfluidic microphysiological systems (MPS) entered the academic scene more than 15 years ago and were considered an enabling technology to human (patho)biology in vitro and, therefore, provide alternative approaches to laboratory animals in pharmaceutical drug development and academic research. Nowadays, the field generates more than a thousand scientific publications per year. Despite the MPS hype in academia and by platform providers, which says this technology is about to reshape the entire in vitro culture landscape in basic and applied research, MPS approaches have neither been widely adopted by the pharmaceutical industry yet nor reached regulated drug authorization processes at all. Here, 46 leading experts from all stakeholders - academia, MPS supplier industry, pharmaceutical and consumer products industries, and leading regulatory agencies - worldwide have analyzed existing challenges and hurdles along the MPS-based assay life cycle in a second workshop of this kind in June 2019. They identified that the level of qualification of MPS-based assays for a given context of use and a communication gap between stakeholders are the major challenges for industrial adoption by end-users. Finally, a regulatory acceptance dilemma exists against that background. This t4 report elaborates on these findings in detail and summarizes solutions how to overcome the roadblocks. It provides recommendations and a roadmap towards regulatory accepted MPS-based models and assays for patients' benefit and further laboratory animal reduction in drug development. Finally, experts highlighted the potential of MPS-based human disease models to feedback into laboratory animal replacement in basic life science research.BACKGROUND Multiple sclerosis (MS) is often associated with fatigue, with an increased prevalence of sleep disorders compared to the general population, notably restless legs syndrome (RLS). MCC950 The aim of this study was to evaluate the prevalence and severity of RLS as well the co-occurrence of spinal demyelination lesions in patients with MS in Lebanon. METHODS In this cross-sectional study, we consulted the MS database of the Lebanese association against Multiple Sclerosis and sent out questionnaires to 300 MS patients to screen then confirm the presence of RLS. The final sample included 28 MS participants with confirmed RLS. We conducted further questionnaires to collect demographic data, screen for comorbidities, gather spinal MRI results, and evaluate the severity of both diseases (using the EDSS and the JHRLSS). RESULTS Prevalence of RLS was 15% among MS patients in our study. 46.4% of RLS-affected MS patients had spinal cord demyelination lesions on their MRIs. Participants with MRI lesions had a lower severity score on the JHRLSS (p = 0.088). No association was found between the EDSS results and JHRLSS, demographic data, or comorbidities. CONCLUSION Restless legs syndrome is commonly found among patients with multiple sclerosis in Lebanon, is underdiagnosed, and ought to be systematically evaluated for in order to improve the patients' quality of life. OBJECTIVES This study aimed to compare the EuroQol 5-dimension 5-level questionnaire (EQ-5D-5L), the visual analogue scale (VAS), and the Kidney Disease Quality of Life 36-Item Short-Form Survey (KDQOL-36) scores of Thai continuous ambulatory peritoneal dialysis (CAPD) and automated peritoneal dialysis (APD) patients and to compare the utility scores with the EQ-5D-5L and VAS scores of caregivers. METHODS This was a cross-sectional study completed between April 2016 and May 2017. In total, 34 CAPD patients, 30 APD patients, and their caregivers were recruited from a large university hospital in Thailand. A trained interviewer conducted face-to-face interviews. We collected demographic data and used the KDQOL-36 and EuroQol questionnaires (EQ-5D-5L and VAS) to assess the health-related quality of life. Caregivers were asked to assess their own health status using the EQ-5D-5L and VAS. RESULTS The EQ-5D-5L and VAS responses of the CAPD and APD patients and their caregivers were not significantly different (P > .05). More than 50% of both patient groups had mobility problems, whereas most patients had no problems with self-care, doing usual activities, pain or discomfort, and anxiety or depression. As for the KDQOL-36, the physical and mental component summaries were not significantly different, and neither were the scores for all of the kidney disease-specific dimensions, including symptoms or problems, effects of kidney disease, and burden of kidney disease (all were P > .05). CONCLUSIONS The results indicated that the quality of life of CAPD and APD patients and their caregivers were mostly equivalent. A further longitudinal study of utility score assessments of the differences in modality would be advantageous.