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Unlabelled: Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease which has no cure, so the treatment will be symptomatic in a Multidisciplinary Unit. It is composed of professionals, experts in patient care, with an interdisciplinary vision in order to act in a coordinated manner depending on the different situations which may arise over the course of the disease. There are several studies showing improved survival in patients treated within the framework of a multidisciplinary team compared to treatment by isolated specialties. An ALS Multidisciplinary Unit was created in 2004 in the University Hospital of Bellvitge (HUB). It is composed of a neurologist, pulmonologist, nutritionist, endocrinologist, rehabilitation, physical therapist, psychologist, social worker, nurse manager, speech therapist and an administrative worker. To assess the impact of the multidisciplinary care of our program 418 patients diagnosed with ALS were evaluated, 84 patients who had been treated by general neurology and 334 who had been treated under a model of multidisciplinary care. Patients who were treated in the unit of multidisciplinary care had a median survival of 1246 days (IC 1109-1382), 104 days above the median 1148 days of those followed by a general neurology consultation (CI 998-1297). This difference was statistically significant (log-rank 10,8; p= 0.008). This benefit was independent of having received treatment with riluzole, non-invasive mechanical ventilation or percutaneous gastrostomy. Nutritional assessment was performed on the first visit and all subsequent controls. It is important to do anthropometric measurements and detect unintentional weight loss and its possible precipitating causes in order to establish the appropriate nutritional treatment. The exploration of dysphagia allows a determination of the appropriate dietary advice, the introduction of thickeners to adjust the texture of food or nutritional supplementation with high-calorie formulas to prevent or correct weight loss. If these measures are not sufficient or there is the risk of failure of respiratory function, early gastrostomy placement will be indicated. The analysis of 140 ALS patients (92 controls and 48 with radiologic percutaneous gastrostomy) showed no difference in mean survival time between groups (32 vs 33.9 months, log Rank 1.86 p=0.39). Any patient had major complications. Despite not find changes in survival, the use of gastrostomy should be understood as a treatment to improve the quality of life and well-being of the patient. Psychosocial support of the person and the family environment is essential to integrate all the changes and situations that arise in the course of the disease. This should start from diagnosis as early intervention contributes to improved training, preventing situations of deterioration and helping coping with the dependency process. It is also possible to use technology and social media to complement the classic care model. In the case of the HUB ALS Multidisciplinary Unit, affected individuals and their families have the resources of the Aula Paciente and ALS blog, created with the objective of providing opportunities for dialogue between patients, families and caregivers. The satisfaction degree of the patients with the care provided by the ALS Multidisciplinary Unit on service accessibility, information received and the quality of care was assessed globally as good in 52.8% or very good in 29, 2% of patients.Conclusion: Attention for the ALS affected person must be considered within the framework of a multidisciplinary team made up of all the professionals who go to intervene throughout the disease process in order to provide increased survival with the best care and quality of life. [ABSTRACT FROM AUTHOR]

Food-grade titanium dioxide (E171) and zinc oxide nanoparticles (ZnO NPs) are common food additives for human consumption. We examined multi-organ toxicity of both compounds on Wistar rats orally exposed for 90 days. Rats were divided into three groups: (1) control (saline solution), (2) E171-exposed, and (3) ZnO NPs-exposed. Histological examination was performed with hematoxylin-eosin (HE) staining and transmission electron microscopy (TEM). Ceramide (Cer), 3-nitrotyrosine (NT), and lysosome-associated membrane protein 2 (LAMP-2) were detected by immunofluorescence. Relevant histological changes were observed: disorganization, inflammatory cell infiltration, and mitochondrial damage. Increased levels of Cer, NT, and LAMP-2 were observed in the liver, kidney, and brain of E171- and ZnO NPs-exposed rats, and in rat hearts exposed to ZnO NPs. E171 up-regulated Cer and NT levels in the aorta and heart, while ZnO NPs up-regulated them in the aorta. Both NPs increased LAMP-2 expression in the intestine. In conclusion, chronic oral exposure to metallic NPs causes multi-organ injury, reflecting how these food additives pose a threat to human health. Our results suggest how complex interplay between ROS, Cer, LAMP-2, and NT may modulate organ function during NP damage.

Background: Metallic nanoparticles (NPs) are widely used as food additives for human consumption. NPs reach the bloodstream given their small size, getting in contact with all body organs and cells. NPs have adverse effects on the respiratory and intestinal tract; however, few studies have focused on the toxic consequences of orally ingested metallic NPs on the cardiovascular system. Here, the effects of two food-grade additives on the cardiovascular system were analyzed., Methods: Titanium dioxide labeled as E171 and zinc oxide (ZnO) NPs were orally administered to Wistar rats using an esophageal cannula at 10 mg/kg bw every other day for 90 days. We evaluated cardiac cell morphology and death, expression of apoptotic and autophagic proteins in cardiac mitochondria, mitochondrial dysfunction, and concentration of metals on cardiac tissue., Results: Heart histology showed important morphological changes such as presence of cellular infiltrates, collagen deposition and mitochondrial alterations in hearts from rats exposed to E171 and ZnO NPs. Intracellular Cyt-C levels dropped, while TUNEL positive cells increased. No significant changes in the expression of inflammatory cytokines were detected. Both NPs altered mitochondrial function indicating cardiac dysfunction, which was associated with an elevated concentration of calcium. ZnO NPs induced expression of caspases 3 and 9 and two autophagic proteins, LC3B and beclin-1, and had the strongest effect compared to E171., Conclusions: E171 and ZnO NPs induce adverse cardiovascular effects in rats after 90 days of exposure, thus food intake containing these additives, should be taken into consideration, since they translocate into the bloodstream and cause cardiovascular damage., (© 2023. The Author(s).)

Zinc oxide nanoparticles (ZnO NPs) are widely used in the cosmetic industry. They are nano-optical and nano-electrical devices, and their antimicrobial properties are applied in food packaging and medicine. ZnO NPs penetrate the body through inhalation, oral, and dermal exposure and spread through circulation to various systems and organs. Since the cardiovascular system is one of the most vulnerable systems, in this work, we studied ZnO NPs toxicity in H9c2 rat cardiomyoblasts. Cardiac cells were exposed to different concentrations of ZnO NPs, and then the morphology, proliferation, viability, mitochondrial membrane potential (ΔΨm), redox state, and protein expression were measured. Transmission electron microscopy (TEM) and hematoxylin-eosin (HE) staining showed strong morphological damage. ZnO NPs were not observed inside cells, suggesting that Zn 2+ ions were internalized, causing the damage. ZnO NPs strongly inhibited cell proliferation and MTT reduction at 10 and 20 μg/cm 2 after 72 h of treatment. ZnO NPs at 20 μg/cm 2 elevated DCF fluorescence, indicating alterations in the cellular redox state associated with changes in ΔΨm and cell death. ZnO NPs also reduced the intracellular expression of troponin I and atrial natriuretic peptide. ZnO NPs are toxic for cardiac cells; therefore, consumption of products containing them could cause heart damage and the development of cardiovascular diseases.

Cardiovascular diseases are the leading cause of death worldwide. Food-grade TiO 2 (E171) is the most widely used additive in the food industry. Existing evidence shows TiO 2 nanoparticles reach systemic circulation through biological barriers, penetrate cell membranes, accumulate in cells of different organs, and cause damage; however, their effects on cardiac cells and the development of heart diseases are still unexplored. Therefore, in this work, we tested E171 toxicity in rat cardiomyoblasts and hearts. E171 internalization and impact on cell viability, proliferation, mitochondria, lysosomes, F-actin distribution, and cell morphology were evaluated in H9c2 cells. Additionally, effects of E171 were measured on cardiac function in ex vivo rat hearts. E171 was uptaken by cells and translocated into the cytoplasm. E171 particles changed cell morphology reducing proliferation and metabolic activity. Higher caspase-3 and caspase-9 expression as well as Tunel-positive cells induced by E171 exposure indicate apoptotic death. Mitochondrial and lysosome alterations resulting from mitophagy were detected after 24 and 48 h exposure, respectively. Additionally, high E171 concentrations caused rearrangements of the F-actin cytoskeleton. Finally, hearts exposed to E171 showed impaired cardiac function. These results support E171 toxicity in cardiac cells in vitro altering cardiac function in an ex vivo model, indicating that consumption of this food additive could be toxic and may lead to the development of cardiovascular disease., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)