Paradoxical lucidity: A potential paradigm shift for the neurobiology and treatment of severe dementias

Unexpected cognitive lucidity and communication in patients with severe dementias, especially around the time of death, have been observed and reported anecdotally. Here, we review what is known about this phenomenon, related phenomena that provide insight into potential mechanisms, ethical implications, and methodologic considerations for systematic investigation. We conclude that paradoxical lucidity, if systematically confirmed, challenges current assumptions and highlights the possibility of networkâ level return of cognitive function in cases of severe dementias, which can provide insight into both underlying neurobiology and future therapeutic possibilities.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153062/1/alzjjalz201904002.pd

Workers’ individual and dyadic coping with the COVID-19 health emergency: A cross cultural study

The aim of this study was to examine workers’ psychological distress during the COVID-19 pandemic as a function of their individual coping, dyadic coping, and work-family conflict. We also tested the moderating role of gender and culture in these associations. To achieve this aim, we run HLM analyses on data from 1521 workers cohabiting with a partner, coming from six countries (Italy, Spain, Malta, Cyprus, Greece, and Russia) characterized by various degrees of country-level individualism/collectivism. Across all six countries, findings highlighted that work-family conflict as well as the individual coping strategy social support seeking were associated with higher psychological distress for workers, while the individual coping strategy positive attitude and common dyadic coping were found to be protective against workers’ psychological distress. This latter association, moreover, was stronger in more individualistic countries. © The Author(s) 2022.NSh-2722.2020.6; CSO 2017–84,634-R, R106450036; Ministerio de Ciencia e Innovación, MICINN; Council on grants of the President of the Russian FederationThis overall research was funded by a grant from the Commissione Strategie di Ricerca – Università Cattolica del Sacro Cuore (protocol n. R106450036) awarded to Claudia Manzi. Data collection by the following researchers was supported by grants as follows: Gerardo Meil (grant CSO 2017–84,634-R from the Spanish Ministry of Science and Innovation); Anna Bagirova (grant NSh-2722.2020.6 from the Council on grants of the President of the Russian Federation)

Olives and olive oil are sources of electrophilic fatty acid nitroalkenes

Extra virgin olive oil (EVOO) and olives, key sources of unsaturated fatty acids in the Mediterranean diet, provide health benefits to humans. Nitric oxide (•NO) and nitrite (NO2-)-dependent reactions of unsaturated fatty acids yield electrophilic nitroalkene derivatives (NO 2-FA) that manifest salutary pleiotropic cell signaling responses in mammals. Herein, the endogenous presence of NO2-FA in both EVOO and fresh olives was demonstrated by mass spectrometry. The electrophilic nature of these species was affirmed by the detection of significant levels of protein cysteine adducts of nitro-oleic acid (NO2-OA-cysteine) in fresh olives, especially in the peel. Further nitration of EVOO by NO2- under acidic gastric digestive conditions revealed that human consumption of olive lipids will produce additional nitro-conjugated linoleic acid (NO2-cLA) and nitro-oleic acid (NO2-OA). The presence of free and protein-adducted NO2-FA in both mammalian and plant lipids further affirm a role for these species as signaling mediators. Since NO2-FA instigate adaptive anti-inflammatory gene expression and metabolic responses, these redox-derived metabolites may contribute to the cardiovascular benefits associated with the Mediterranean diet. © 2014 Fazzari et al

Caracterización nutricional y en compuestos bioactivos de trigo nacional.

El trigo ocupa un lugar de privilegio en la cultura alimentaria nacional y en el equilibrio de la dieta humana. Es el cereal más consumido y constituye la primera fuente de energía alimentaria de la población. En esta publicación se presentan los resultados y conclusiones en relación a la calidad nutricional y en compuestos bioactivos de trigo nacional en diferentes genotipos y ambientes y a su actividad antioxidante en ensayos "in vivo"

Macrophage activation induces formation of the anti-inflammatory lipid cholesteryl-nitrolinoleate

Nitroalkene derivatives of fatty acids act as adaptive, anti-inflammatory signalling mediators, based on their high-affinity PPARγ (peroxisome-proliferator-activated receptor γ) ligand activity and electrophilic reactivity with proteins, including transcription factors. Although free or esterified lipid nitroalkene derivatives have been detected in human plasma and urine, their generation by inflammatory stimuli has not been reported. In the present study, we show increased nitration of cholesteryl-linoleate by activated murine J774.1 macrophages, yielding the mononitrated nitroalkene CLNO2 (cholesteryl-nitrolinoleate). CLNO2 levels were found to increase ∼20-fold 24 h after macrophage activation with Escherichia coli lipopolysaccharide plus interferon-γ; this response was concurrent with an increase in the expression of NOS2 (inducible nitric oxide synthase) and was inhibited by the •NO (nitric oxide) inhibitor L-NAME (NG-nitro-L-arginine methyl ester). Macrophage (J774.1 and bone-marrow-derived cells) inflammatory responses were suppressed when activated in the presence of CLNO2 or LNO2 (nitrolinoleate). This included: (i) inhibition of NOS2 expression and cytokine secretion through PPARγ and •NO-independent mechanisms; (ii) induction of haem oxygenase-1 expression; and (iii) inhibition of NF-κB (nuclear factor κB) activation. Overall, these results suggest that lipid nitration occurs as part of the response of macrophages to inflammatory stimuli involving NOS2 induction and that these by-products of nitro-oxidative reactions may act as novel adaptive down-regulators of inflammatory responses

Macrophage activation induces formation of the anti-inflammatory lipid cholesteryl-nitrolinoleate

Nitroalkene derivatives of fatty acids act as adaptive, anti-inflammatory signalling mediators, based on their high-affinity PPARγ (peroxisome-proliferator-activated receptor γ) ligand activity and electrophilic reactivity with proteins, including transcription factors. Although free or esterified lipid nitroalkene derivatives have been detected in human plasma and urine, their generation by inflammatory stimuli has not been reported. In the present study, we show increased nitration of cholesteryl-linoleate by activated murine J774.1 macrophages, yielding the mononitrated nitroalkene CLNO2 (cholesteryl-nitrolinoleate). CLNO2 levels were found to increase ∼20-fold 24 h after macrophage activation with Escherichia coli lipopolysaccharide plus interferon-γ; this response was concurrent with an increase in the expression of NOS2 (inducible nitric oxide synthase) and was inhibited by the •NO (nitric oxide) inhibitor L-NAME (NG-nitro-L-arginine methyl ester). Macrophage (J774.1 and bone-marrow-derived cells) inflammatory responses were suppressed when activated in the presence of CLNO2 or LNO2 (nitrolinoleate). This included: (i) inhibition of NOS2 expression and cytokine secretion through PPARγ and •NO-independent mechanisms; (ii) induction of haem oxygenase-1 expression; and (iii) inhibition of NF-κB (nuclear factor κB) activation. Overall, these results suggest that lipid nitration occurs as part of the response of macrophages to inflammatory stimuli involving NOS2 induction and that these by-products of nitro-oxidative reactions may act as novel adaptive down-regulators of inflammatory responses

Conjugated linoleic acid is a preferential substrate for fatty acid nitration

The oxidation and nitration of unsaturated fatty acids by oxides of nitrogen yield electrophilic derivatives that can modulate protein function via post-translational protein modifications. The biological mechanisms accounting for fatty acid nitration and the specific structural characteristics of products remain to be defined. Herein, conjugated linoleic acid (CLA) is identified as the primary endogenous substrate for fatty acid nitration in vitro and in vivo, yielding up to 105 greater extent of nitration products as compared with bis-allylic linoleic acid. Multiple enzymatic and cellular mechanisms account for CLA nitration, including reactions catalyzed by mitochondria, activated macrophages, and gastric acidification. Nitroalkene derivatives of CLA and their metabolites are detected in the plasma of healthy humans and are increased in tissues undergoing episodes of ischemia reperfusion. Dietary CLA and nitrite supplementation in rodents elevates NO2-CLA levels in plasma, urine, and tissues, which in turn induces heme oxygenase-1 (HO-1) expression in the colonic epithelium. These results affirm that metabolic and inflammatory reactions yield electrophilic products that can modulate adaptive cell signaling mechanisms.Fil: Bonacci, Gustavo Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina. Univeristy Of Pittsburgh. School Of Medicine. Department Of Pharmacology And Chemical Biology; Estados UnidosFil: Baker, Paul R. S.. Univeristy Of Pittsburgh. School Of Medicine. Department Of Pharmacology And Chemical Biology; Estados UnidosFil: Salvatore, Sonia Rosana. Univeristy Of Pittsburgh. School Of Medicine. Department Of Pharmacology And Chemical Biology; Estados UnidosFil: Shores, Darla. University of Pittsburgh; Estados UnidosFil: Khoo, Nicholas K. H.. Univeristy Of Pittsburgh. School Of Medicine. Department Of Pharmacology And Chemical Biology; Estados UnidosFil: Koenitzer, Jeffrey R.. Univeristy Of Pittsburgh. School Of Medicine. Department Of Pharmacology And Chemical Biology; Estados UnidosFil: Vitturi, Dario A.. Univeristy Of Pittsburgh. School Of Medicine. Department Of Pharmacology And Chemical Biology; Estados UnidosFil: Woodcock, Steven R.. Univeristy Of Pittsburgh. School Of Medicine. Department Of Pharmacology And Chemical Biology; Estados UnidosFil: Golin-Bisello, Franca. Univeristy Of Pittsburgh. School Of Medicine. Department Of Pharmacology And Chemical Biology; Estados UnidosFil: Cole, Marsha P.. Univeristy Of Pittsburgh. School Of Medicine. Department Of Pharmacology And Chemical Biology; Estados UnidosFil: Watkins, Simon. University of Pittsburgh; Estados UnidosFil: St. Croix, Claudette. University of Pittsburgh; Estados UnidosFil: Batthyany, Carlos I.. Instituto Pasteur; Uruguay. Univeristy Of Pittsburgh. School Of Medicine. Department Of Pharmacology And Chemical Biology; Estados UnidosFil: Freeman, Bruce A.. Univeristy Of Pittsburgh. School Of Medicine. Department Of Pharmacology And Chemical Biology; Estados UnidosFil: Schopfer, Francisco J.. Univeristy Of Pittsburgh. School Of Medicine. Department Of Pharmacology And Chemical Biology; Estados Unido